Electroacupuncture Stimulation Research Articles

Effect of different electrical current intensities of electroacupuncture preconditioning on cardiac function and macrophage polarization in mice with acute myocardial ischemia

To observe the effect of different intensities of electroacupuncture (EA) preconditioning on car-diac function and polarization state of macrophages in mice with acute myocardial ischemia (AMI), so as to explore its possible mechanism underlying improvement of AMI. A total of 50 male C57BL/6J mice were randomly divided into sham ope-ration, AMI model, and EA pretreatment groups (0.5 mA, 1 mA, 3 mA subgroups), with 10 mice in each group/subgroup. The mice in the EA pretreatment groups were subjected to EA stimulation of bilateral "Neiguan"(PC6) with 0.5, 1.0 and 3 mA respectively and frequency of 2 Hz/15 Hz for 20 min, once a day, for 3 days. The acute myocardial ischemia model was established by ligating the anterior descending branch (ADB) of the left coronary artery, while the sham operation only had a surgical suture trans-passed below the ADB but without ligation. The myocardial infarction area was measured after TTC staining, and the cardiac function ［left ventricular ejection fraction (EF), short-axis contraction rate (FS)］ was detected by using echocardiography. The M1 macrophages were labeled with CD11b+F480+CD206low, M2 macrophages were labeled with CD11b+F480+CD206high and detected by using flow cytometry, and the expression levels of myocardial interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4) proteins were detected by using Western blot. Compared with the sham operation group, the model group had a significant increase in the infarction area (P<0.000 1), number of cardiac macrophages and percentage of M1 type macrophages (P<0.000 1), and the expression levels of myocardial IL-1β, TNF-α, TLR4 proteins (P<0.001, P<0.01), and a remarkable decrease in the levels of EF, FS and the percentage of M2 type macrophages (P<0.000 1). In contrast to those of the model group, the area of myocardial infarction (P<0.000 1, P<0.01), expression levels of myocardial IL-1β, TNF-α, TLR4 proteins (P<0.01, P<0.05, P<0.001) in the 0.5 mA, 1 mA and 3 mA groups, number of macrophages and percentage of M1 macrophages (P<0.05) in the 1 mA group were significantly decreased, while the levels of EF and FS (P<0.000 1, P<0.05, P<0.001) in the 3 EA groups, and percentage of M2 macrophage (P<0.05) in the 1 mA group were significantly increased. Comparison among the 3 EA groups displayed that the effects of 1 mA group were significantly superior to those of 0.5 and 3 mA groups in up-regulating EF and FS (P<0.01, P<0.001), and in down-regulating the area of infarct myocardium (P<0.01, P<0.000 1), and the expression of TLR4 protein (P<0.01), and 0.5 mA group in the expression of IL-1β and TNF-α proteins (P<0.05). EA preconditioning with electrical current intensities of 0.5 mA, 1 mA and 3 mA can effectively reduce myocardial infarction size, improve cardiac function in mice with AMI, which may be related with its effects in reducing the number of cardiac macrophages and down-regulating the expression of myocardial IL-1β, TNF-α and TLR4 proteins. The therapeutic effect of 1 mA is better than that of 0.5 and 3 mA.

Electroacupuncture Activates Neuroplasticity in the Motor Cortex and Corticospinal Tract via the mTOR Pathway in a Rat P-MCAO Model.

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1-C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts.

Adrenal sympathetic nerve mediated the anti-inflammatory effect of electroacupuncture at ST25 acupoint in a rat model of sepsis.

Acupuncture plays a vital anti-inflammatory action in sepsis by activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating the sympathoadrenal medullary pathway and evaluate EA's anti-inflammatory effect on sepsis. To determine the optimum parameter of EA at homotopic acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley rats were evaluated by in vivo electrophysiological recording, and the levels of norepinephrine (NE) and its metabolites normetanephrine (NMN) were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rats were given an intraperitoneal injection of lipopolysaccharide (LPS) to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1β, and IL-10 were evaluated after EA application. We observed that 3mA is the optimal intensity for activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1β and upregulated anti-inflammatory cytokine IL-10 compared to the LPS-treated group. Overall, our data suggested that 3mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect in sepsis.

Effects of electroacupuncture on sexual development and ovarian estrogen receptor β expression in female adolescent obese rats

To observe the effect of electroacupuncture on sexual development and ovarian estrogen receptor β(ER-β) expression in female adolescent obese rats induced by high-fat diet, so as to explore its underlying mechanisms of improving adolescent obesity. Female SD rats (age of 21 days) were randomly divided into control, model and acupuncture groups, with 6 rats in each group. The obese model was established by feeding high-fat diet for 6 weeks. Rats of the acupuncture group received electroacupuncture(2 Hz, 0.5-1.2 mA)stimulation at bilateral "Sanyinjiao"(SP6), "Fenglong"(ST40) and "Zusanli"(ST36) for 30 min, once a day for 14 days. The body mass and abdominal circumference of rats were measured before and after treatment. The contents of serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by ELISA. The number of corpus luteum and follicle were observed by HE staining. The expression levels of ER-β mRNA and protein in ovary were detected by fluorescence quantitative PCR and Western blot, respectively. Compared with the control group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-β mRNA and protein in ovary were significantly increased (P<0.05)in the model group, while the number of mature follicles and corpus luteum increased significantly. Compared with the model group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-β mRNA and protein in ovary were significantly decreased (P<0.05) in the acupuncture group, while the number of mature follicles and corpus luteum decreased significantly. Electroacupuncture can effectively improve the levels of sex hormone and the development of ovary, down-regulate the expression levels of ER-β mRNA and protein in ovary, so as to regulate the process of sexual development of female adolescent obese rats induced by high-fat diet.

Electroacupuncture at Acupoint ST36 (Zusanli) Improves Intestinal Motility Dysfunction Via Increasing the Proportion of Cholinergic Neurons in Rat Ileal Myenteric Ganglia after Severe Acute Pancreatitis.

Using a severe acute pancreatitis (SAP) rat model, the mechanism of electroacupuncture (EA) were studied on the intestinal function of pancreatitis. The SAP models were established by injecting 30% L-ornithine at hourly intervals, and were divided into two groups (14 in each): SAP model group, which was not treated, and EA group, which received EA at ST36 at a frequency of 1-2 Hz and amplitude of 1 mA for 30 min twice a day. Fourteen rats were also included as the control group. After EA, the intestinal propulsion was measured. In the distal ileum myenteric plexus, the density of HuC/D and the proportion of cholinergic neurons were measured using immunohistochemistry. Compared to the SAP model group, the EA group demonstrated significant improvements in intestinal propulsion rates. Furthermore, after EA, the density of myenteric neurons in the ileum returned to normal levels and the proportion of cholinergic neurons was increased compared to the SAP model group. And finally, EA alleviated the damage to the pancreas. Thus, our results suggest that EA stimulation at ST36 can partly restore the enteric neuron function and improve intestinal motility dysfunction, therefore could ameliorate SAP. The enteric nervous system can participate in changes in intestinal motility by affecting cholinergic neurons.

Electroacupuncture of the trigeminal nerve causes N-methyl-D-aspartate receptors to mediate blood-brain barrier opening and induces neuronal excitatory changes.

The blood-brain barrier (BBB) is an important structure for maintaining environmental stability in the central nervous system (CNS). Our previous study showed that specific parameters of electroacupuncture (EA) at the head points Shuigou (GV26) and Baihui (GV20) can open the BBB; however, the mechanism by which stimulation of body surface acupuncture points on the head results in peripheral stimulation and affects the status of the central BBB and the neuronal excitatory changes has not been elucidated. We used laser spectroscopy, the In Vivo Imaging System (IVIS), immunofluorescence and immunoblotting to verified the role of the trigeminal nerve in BBB opening during EA, and we applied the central N-methyl-D-aspartate (NMDA) receptors blocker MK-801 to verify the mediating role of NMDA receptors in EA-induced BBB opening. Next, electroencephalogram (EEG) and in vivo calcium imaging techniques were applied to verify the possible electrical patterns of BBB opening promoted by different intensities of EA stimulation. The results showed that the trigeminal nerve plays an important role in the alteration of BBB permeability promoted by EA stimulation of the head acupoints. Brain NMDA receptors play a mediating role in promoting BBB permeability during EA of the trigeminal nerve, which may affect the expression of the TJ protein occludin, and thus alter BBB permeability. The analysis of the electrical mechanism showed that there was no significant change in the rhythm of local field potentials (LFP) in different brain regions across frequency bands immediately after EA of the trigeminal nerve at different intensities. However, the local primary somatosensory (S1BF) area corresponding to the trigeminal nerve showed a transient reduction in the delta rhythm of LFP with no change in the high-frequency band, and the action potential (spike) with short inter spike interval (ISI) varied with EA intensity. Meanwhile, EA of the trigeminal nerve resulted in rhythmic changes in calcium waves in the S1BF region, which were influenced by different EA intensities. This study provides a research perspective and a technical approach to further explore the mechanism of EA-induced BBB opening and its potential clinical applications.

Research Hotspots and Trends on Acupuncture for Neuropathic Pain: A Bibliometric Analysis from 2002 to 2021.

PurposeIn this study, we aimed to systematically determine the trend, research hotspots, and directions of the future development of acupuncture for neuropathic pain (NP) by bibliometric analysis.MethodsBased on the relevant literature on acupuncture for NP in the databases of Web of Science from January 2002 to December 2021, Citespace software and VOSviewer were used to determine the use of acupuncture for the treatment of NP. The annual publications, countries, authors, research institutions, keywords, co-cited references, and journals were analyzed to explore the research hotspot and development trends in this field.ResultsA total of 1462 records of acupuncture for NP from 2002 to 2021 were obtained. Chingliang Hsieh (20) is the most effective author and Han JS (585 co-citations) is the most influential author. The most productive institutions and countries are Kyung Hee UNIV (88) and China, respectively (480). UNIV Maryland of the USA has the highest centrality (0.12). Evidence-based complementary and alternative medicine (89) is the most prolific journal, and Pain is the most influential journal (4200 co-citations). Ji-sheng Han (2003) is the most frequently cited article (158 co-citations). Electroacupuncture, bee-venom acupuncture, and percutaneous electrical stimulation are the most commonly studied acupuncture types. The analgesic mechanism of acupuncture and acupuncture-neuroimaging was a research hotspot over the years. The clinical evidence of acupuncture for NP should be further studied in the future.ConclusionThe study using bibliometric analysis methods to investigate the publications on acupuncture for NP so as to provide potential research directions in the future.

Electroacupuncture stimulation of HT7 alleviates sleep disruption following acute caffeine exposure by regulating BDNF-mediated endoplasmic reticulum stress in the rat medial septum

Acupuncture stimulation can protect the brain against caffeine-induced sleep disruption. This study investigated whether electroacupuncture stimulation acupuncture point HT7 alleviates sleep disruption by regulating mBDNF and ER stress in the medial septum. Acute exposure to caffeine (15 mg/kg, i.p.) increased the wake time and decreased REM sleep, which HT7 stimulation alleviated. HT7 stimulation ameliorated the acute caffeine exposure-induced increase in the expression of BiP, an endoplasmic reticulum stress response protein, in the rat medial septum. Interestingly, HT7 stimulation induced the expression of mBDNF and pTrkB in the medial septum. The next experiment investigated whether TrkB phosphorylated by HT7 stimulation induced BiP expression in the rat medial septum. Before electroacupuncture stimulation at HT7, ANA-12 was administered to caffeine-treated rats. In rats administered ANA-12 in the medial septum, HT7 stimulation did not reduce BiP expression. These findings suggest that HT7 stimulation improves wake time and REM sleep dysfunction by regulating the BDNF-mediated endoplasmic reticulum stress response in the medial septum. These results indicate that the alleviation of endoplasmic reticulum stress in the medial septum by HT7 stimulation and the subsequent amelioration of insomnia may depend on phosphorylated TrkB activation.

Combined-Acupoint Electroacupuncture Induces Better Analgesia via Activating the Endocannabinoid System in the Spinal Cord.

Electroacupuncture (EA) therapy has been widely reported to alleviate neuropathic pain with few side effects in both clinical practice and animal studies worldwide. However, little is known about the comparison of the therapeutic efficacy among the diverse EA schemes used for neuropathic pain. The present study is aimed at investigating the therapeutic efficacy discrepancy between the single and combined-acupoint EA and to reveal the difference of mechanisms behind them. Electroacupuncture was given at both Zusanli (ST36) and Huantiao (GB30) in the combined group or ST36 alone in the single group. Paw withdrawal mechanical threshold (PWMT) was measured to determine the pain level. Electrophysiology was performed to detect the effects of EA on synaptic transmission in the spinal dorsal horn of the vGlut2-tdTomato mice. Spinal contents of endogenous opioids, endocannabinoids, and their receptors were examined. Inhibitors of CBR (cannabinoid receptor) and opioid receptors were used to study the roles of opioid and endocannabinoid system (ECS) in EA analgesia. We found that combined-acupoint acupuncture provide stronger analgesia than the single group did, and the former inhibited the synaptic transmission at the spinal level to a greater extent than later. Besides, the high-intensity stimulation at ST36 or normal stimulation at two sham acupoints did not mimic the similar efficacy of analgesia in the combined group. Acupuncture stimulation in single and combined groups both activated the endogenous opioid system. The ECS was only activated in the combined group. Naloxone totally blocked the analgesic effect of single-acupoint EA; however, it did not attenuate that of combined-acupoint EA unless coadministered with CBR antagonists. Hence, in the CCI-induced neuropathic pain model, combined-acupoint EA at ST36 and GB30 is more effective in analgesia than the single-acupoint EA at ST36. EA stimulation at GB30 alone neither provided a superior analgesic effect to EA treatment at ST36 nor altered the content of AEA, 2-AG, CB1 receptor, or CB2 receptor compared with the CCI group. Activation of the ECS is the main contributor of the better analgesia by the combined acupoint stimulation than that induced by single acupoint stimulation.

Electroacupuncture Stimulation Suppresses Postoperative Inflammatory Response and Hippocampal Neuronal Injury.

Postoperative cognitive dysfunction (POCD) is consequence of anesthesia and surgery that primarily affects older people. The prevention and treatment of POCD has drawn an increasing attention in recent decades. Here, we established the animal model mimicked POCD after femoral fracture surgery, and analyze the effect of acupuncture stimulation on postoperative cognitive function after femoral fracture surgery. Compared with the mock group, the cognitive function performance was significantly decreased both in the anaesthesia group and the surgery group, between which the symptoms were more severe in the surgery group. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus were observed in the surgery group, but only peripheral inflammation response was detected in the anaesthesia group. These findings indicated the POCD was the synergistic outcome of anaesthesia and surgical stimulation but with different pathogenic mechanism. The surgery with mental tri-needles (surgery+MTN) group outperformed the surgery group in terms of cognitive function performance. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus was significantly reduced by the electroacupuncture stimulation. Our findings indicated the protection of electroacupuncture form POCD after femoral fracture surgery is related to the inhibition of inflammation response and neuron impairment.

Transcriptomic Profiling of Electroacupuncture Regulating the Molecular Network in Hippocampus of Rats with Cerebral Ischemia-Reperfusion Injury.

Objective To explore the mechanism of electroacupuncture stimulation of the hand-taiyin meridian in regulating the molecular network of rats with cerebral ischemia-reperfusion injury based on transcriptomics. Methods Male SD rats were randomly divided into sham operation group, model group, and electroacupuncture (EA) group. Middle cerebral artery embolization/reperfusion injury (MCAO/R) was used to establish the model group and EA group. The sham operation group only performed sham operation without modeling and any intervention, and the model group was bound daily. The EA group received electroacupuncture to stimulate the acupoints of hand-taiyin meridian for 14 days. Then, neurological scores, pathomorphological observations, and Tunel staining were performed. Finally, the affected hippocampus of the rat was used for transcriptome sequencing and RT-PCR detection. Results After electroacupuncture intervention in rats, neurological function scores were improved, and neuronal apoptosis was reduced. The results of transcriptomics showed that a total of 1097 differentially expressed genes were obtained, of which 422 were upregulated and 675 were downregulated. The bioinformatics analysis showed that those differentially expressed genes were related to axon development, neuron projection development, neuron projection morphogenesis, plasma membrane cell projection morphogenesis, cell part morphogenesis, notch signaling pathway, long-term potentiation, MAPK signaling pathway, Hedgehog signaling pathway, and so on. The results of RT-PCR showed that Caspase 9 mRNA increased and BDNF, Grin2a, and PlexinD1 mRNA decreased after electroacupuncture intervention (P < 0.05). Conclusion Electroacupuncture intervention on hand-taiyin meridian may reduce neurological function scores, inhibit neuron apoptosis, and enhance neuronal repair neuroreparation in MCAO/R rats, which may be related to the regulation of genes such as Caspase 9, BDNF, Grin2a, and PlexinD1.

Research on electroacupuncture parameters for knee osteoarthritis based on data mining

BackgroundKnee osteoarthritis, a common degenerative joint disease, has been widely treated by electroacupuncture in recent years. However, there are too many parameters of the treatment currently, resulting in various applications in clinical practice. This study aims to summarize the optimal stimulation parameters of electroacupuncture for knee osteoarthritis in clinical studies by applying data mining techniques.MethodsFour databases including Pubmed, Cochrane Library, Embase, and Web of Science were searched for clinical studies on electroacupuncture treating knee osteoarthritis from 2012 to 2021. A database was established by Microsoft Excel 2020 and analyzed by R Version 4.1.1.ResultsForty-six articles were included according to the established criteria. The most used electroacupuncture stimulation parameters were 0.30 mm × 40 mm needle, continuous wave, low frequency of current (mainly 2 Hz), stimulation duration for 30 min per treatment, and frequency of treatment for once a day. Eighteen acupoints were mentioned and the most used ones include Dubi (ST35), Liangqiu (ST34), Neixiyan (EX-LE4), Xuehai (SP10), Yanglingquan (GB34), and Yinlingquan (SP9), and those most generally used acupoints are closely arranged on the Stomach Channel of Foot Yangming. Cluster analysis showed two groups, one for obligatory acupoints and one for adjunctive ones. The association analysis showed the most supported acupoint pair was Liangqiu (ST34) and Xuehai (SP10).ConclusionsContinuous wave, low frequency of current (2 Hz), 30-min stimulation, and local acupoint selection are frequently used for electroacupuncture treating knee osteoarthritis. Due to the limitations of this study, further research and more standardized, multi-centered, and large-sample clinical trials should be conducted to provide more convincing evidence.

Mechanism of Electroacupuncture Analgesia on Nicotine Withdrawal-Induced Hyperalgesia in a Rat Model.

Purpose This study aimed to investigate the analgesic effect and mechanism of electroacupuncture (EA) in nicotine withdrawal-induced hyperalgesia rats. Methods Behavioral testing was conducted twice a week for 7 weeks during nicotine administration using von Frey filaments. Electroacupuncture at the bilateral “Zusanli” and “Taichong” points was applied daily for 3 days during nicotine withdrawal. Western blot analysis and immunohistology were used to determine expression levels of pain-related factors in the spinal cord and midbrain periaqueductal gray (PAG). Results Behavioral tests showed that electroacupuncture had a significant analgesic effect on nicotine withdrawal-induced hyperalgesic rats. Western blot results demonstrated that, in hyperalgesic rats, the expressions of nicotinic acetylcholine receptors (subunits: nAChR α7, α4, or β2) decreased in the spinal cord, nAChR α7, and β2 decreased in PAG. The proinflammatory factor cyclooxygenase 2 (COX2) and the activated microglia (ionized calcium-binding adaptor molecule 1, Iba1 positive cells) increased in the spinal cord and PAG compared to controls. After electroacupuncture treatment, nAChR α7 and nAChR β2 expressions increased significantly, and COX2 and Iba1 expressions decreased in the spinal cord. Compared with the nonelectroacupuncture nicotine withdrawal group, electroacupuncture stimulation increased the expression of nAChR α7 and nAChR α4 in the PAG of rats with electroacupuncture. Immunohistochemical results confirmed that electroacupuncture reversed nicotine withdrawal-induced changes in nAChR α7 positive neurons and Iba1-positive microglia in the dorsal horn of the spinal cord. Conclusion Electroacupuncture treatment has an analgesic effect on nicotine withdrawal-induced pain in nicotine-dependent rats. The mechanism of analgesia of the electroacupuncture treatment relates to the increased expression of nAChR α7 and nAChR β2 proteins in the spinal cord, nAChR α7 in the PAG, and decreased expression of Iba1 and COX2 protein in the spinal cord.

Electroacupuncture preconditioning improves pulmonary function via inhibiting inflammatory response and up-regulating expression of ACE2 and Ang (1-7) in lipopolysaccharide-induced acute lung injury rats

To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) pretreatment on lung functions, inflammatory response, and levels of angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) ［Ang (1-7)］ in rats with sepsis-induced acute lung injury (ALI), so as to explore its mechanisms underlying improvement of ALI. Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The sepsis-related ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Rats of the EA group received EA (4 Hz/20 Hz, 1-3 mA) stimulation at bilateral ST36 for 30 min, once each day, for 7 days before modeling. The lung functions including forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1) and FEV0.3 were detected using a respiratory function detector for small animals at 3 h after modeling. The bronchoalveolar lavage fluid (BALF) was collected for assaying the contents of Ang (1-7), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) using ELISA. The lung wet/dry weight (W/D) ratio, FEV0.1/FVC, and FEV0.3/FVC were calculated. The histopathological changes of lung tissues were displayed by hematoxylin-eosin (H.E.) staining. The expression of ACE2 and mitochondrial assembly receptor (MasR) mRNAs and proteins in the lung tissue was detected by fluorescence quantitative real-time PCR and Western blot, separately. Following modeling, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and the expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly decreased (P<0.01), while the level of W/D ratio and TNF-α and IL-1β contents in the BALF significantly increased (P<0.01) in the model group relevant to the normal group. In comparison with the model group, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly increased (P<0.05, P<0.01), whereas the level of W/D ratio, and TNF-α and IL-1β contents in the BALF were significantly decreased (P<0.05, P<0.01) in the EA group. H.E. staining showed pulmonary interstitial edema and alveolar septum thickening with severe inflammatory cell infiltration in the model group, which was relatively milder in the EA group. EA preconditioning at ST36 can improve pulmonary function in sepsis-related ALI rats, which may be related to its effects in inhibiting inflammatory response and up-regulating ACE2 and MasR expression and Ang (1-7) content in the lung tissue.

Effect of electroacupuncture of "Zusanli"(ST36) and "Guanyuan" (CV4) on apoptosis and expression of apoptosis-related proteins of synoviocytes in adjuvant-induced arthritis rats

To observe the effect of electroacupuncture (EA) of "Zusanli"(ST36) and "Guanyuan"(CV4) on the apoptosis rate of synoviocytes and protein expression of Fas, FasL and Caspase-3 in synovial tissue of adjuvant-induced arthritis (AIA) rats, so as to explore its mechanisms underlying improvement of rheumatoid arthritis （RA）. A total of 24 rats were randomly divided into normal, model, medication and EA groups, with 6 rats in each group. The AIA model was established by injection of complete Freund's adjuvant (CFA, 0.1 mL) into the left hindlimb paw. The rats in the medication group received intraperitoneal injection of 0.35 mg/kg of methotrexate, twice a week for 4 weeks. The rats in the EA group received EA stimulation of ST36 and CV4 (20 Hz/50 Hz, 1 mA) for 20 min, 6 times a week for 4 weeks. The left hind paw volume was measured using a paw volume meter, and histopathological changes of synovial tissue were observed by light microscope after H.E. staining. The serum contents of tumor necrosis factor-α（TNF-α） and interleukin-1 （IL-1） were measured by ELISA. The apoptosis of synoviocytes was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL), and the expression of apoptosis-associated proteins Fas, FasL and Caspase-3 in synovium were detected by Western blot. Compared with the normal group, the left hind paw volume from day 3 to 24 after administration of CFA, serum IL-1 and TNF-α contents were significantly increased (P<0.01), while the expressions of Fas, FasL and Caspase-3 proteins and apoptotic rate of synoviocytes were significantly decreased in the model group (P<0.01). In comparison with the model group, the paw volume from day 17 to 24 after modeling, the serum IL-1 and TNF-α contents were significantly reduced (P<0.01), while the apoptotic rate of synoviocytes, expressions of Fas protein in both medication and EA groups, Caspase-3 protein in the acupuncture group and FasL protein in the medication group were increased (P<0.01, P<0.05). Compared with the medication group, the expression of FasL protein was decreased in EA group (P<0.05). H.E. stain showed obvious hyperplasia of the synovial lining layer, and disordered arrangement of synovial cells, with edema and enlargement in some cells in the model group, which was relatively milder in both medication and EA groups. EA of ST36 and CV4 can promote the apoptosis of synoviocytes and the expressions of Fas and FasL proteins in AIA rats, which may contribute to its role in relieving synovitis through activating Fas/FasL signaling.

Effectiveness and Safety of Electroacupuncture for Depression: A Systematic Review and Meta-Analysis.

Purpose The purpose of this systematic review and meta-analysis was to comprehensively evaluate the efficacy and safety of electroacupuncture as an effective adjunctive therapy for patients with depression. Methods Randomized controlled trials (RCTs) about the treatment of depression by electroacupuncture therapy from inception to September 2021 were searched and collected in eight databases. HAMD, SDS, and Adverse Reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each outcome was assessed through the Grading of Recommendations Assessment and the Development and Evaluation approach. Stata 15.0 software was used for data analysis. Results A total of 16 depression-related RCTs were included in this meta-analysis. For the main outcome, electroacupuncture significantly reduced HAMD scores (I2:0.0%, SMD: −2.28% (95% CI−3.16 to −1.39)), and the quality of evidence was moderate. The improvement effect of electroacupuncture plus antidepressants was better than that of western drugs in patients with depression (I2:26.2%, SMD: −1.18% (95% CI−1.42 to −0.94)), and the quality of evidence was moderate. Electroacupuncture significantly reduced HAMD scores without significant heterogeneity (I2:0.0%, SMD: −3.76% (95%CI−5.78−1.73)). Studies with very low quality of evidence found that electroacupuncture was as effective as antidepressants in reducing SDS scores (I2:36.4%, WMD: −1.15% (95%CI−2.93–0.63)), and electroacupuncture was found to be more effective than sham electroacupuncture stimulation as well. Moderate quality evidence showed no statistical difference between electroacupuncture plus antidepressants/electroacupuncture and antidepressants (I2:0%, RR:1.05% (95%CI 0.73 to 1.53)). Conclusions Our meta-analysis shows that electroacupuncture reduces HAMD scores. It is suggested to use electroacupuncture plus antidepressants to improve the curative effect and effectively reduce drug side effects.

Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine.

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut–brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut–brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.

Alteration of brain functional networks induced by electroacupuncture stimulation in rats with ischemia–reperfusion: An independent component analysis

Motor dysfunction is the major sequela of ischemic stroke. Motor recovery after stroke has been shown to be associated with remodeling of large-scale brain networks, both functionally and structurally. Electroacupuncture (EA) is a traditional Chinese medicine application that has frequently been recommended as an alternative therapy for ischemic stroke and is reportedly effective for alleviating motor symptoms in patients. In the present study, the effect of EA on the alterations of functional resting state networks (RSNs) was explored after middle cerebral artery occlusion/reperfusion (MCAO/R) injury using resting-state functional MRI. Rats were randomly assigned to three groups, including the sham group, MCAO/R group and MCAO/R+EA group. The ladder rung walking test was conducted prior to and after modeling to assess behavioral changes. RSNs were identified based on the independent component analysis (ICA) performed on the fMRI data from groups. EA treatment effectively reduced the occurrence of contralateral forelimb foot faults. Furthermore, our results suggested the disrupted function of the whole-brain network following ischemic stroke and the modulatory effect of acupuncture. The sensorimotor network (SMN), interoceptive network (IN), default mode network (DMN) and salience network (SN) were related to the therapeutic effect of EA on stroke recovery. Collectively, our findings confirmed the effect of EA on motor function recovery after cerebral ischemia reperfusion and shed light on the assessment of EA intervention-induced effects on brain networks. This study provides neuroimaging evidence to explain the therapeutic effects of EA in ischemic stroke and will lay the groundwork for further studies.

Effects of electroacupuncture on behaviors and expressions of SYN and PSD95 in hippocampus of rats with post-traumatic stress disorder

Objective: Electroacupuncture (EA) in the treating principle of “soothing the liver and regulating the kidney” was applied to intervion the rats with post-traumatic stress disorder (PTSD), and its effect on anxiety-like behavior, spatial learning and memory ability, and expressions of synaptophysin (SYN) and postsynaptic dense 95 (PSD95) in hippocampus of rats were observed to explore the underlying mechanism.Methods: Twenty-four male SD rats were randomly divided into control group, model group, and EA group, with 8 rats in each group. There was no intervention in the control group. The rest 16 rats were prepared for modeling. The single-prolonged stress & shock (SPS&S) method was used to establish the PTSD models. There was no intervention in the model group after modeling. In the EA group, “Bǎihuì (百会GV20)”“ Shéntíng (神庭GV24)”“Gānshū (肝俞BL18)”“Shènshū (肾俞BL23)” were manipulated with EA stimulation, intensity 1 mA, frequency 2/100 Hz, disperse-dense wave, and treatment was performed once a day, 20 min each time, for a total of 21 days. Open field test, elevated plus maze and Morris water maze tests were used to observe the behavioral differences of rats in each group. Immunohistochemical method was used to observe the differences of positive expressions of proteins SYN and PSD95 in hippocampus.Results: In the open field test, compared with the control group, the total traveling distance, the percentage of the time spent in the central cell and the numbers of the central cells crossing in the model group were all decreased (all P < 0.05). Compared with the model group, these indicators in the EA group were significantly all increased (all P < 0.05). In the elevated plus maze test, compared with the control group, the percentages of open arm staying time and entering times in the model group were both decreased (both P < 0.05). Compared with the model group, these indicators in the EA group were both significantly increased (both P < 0.05). The results of Morris water maze test showed that compared with the control group, the escape latency time and travelled distance of rats in the model group were all increased from day1 to day 4 (all P < 0.05), and the percentage of staying time in the target quadrant was decreased (P < 0.05). Compared with the model group, the escape latency time and travelled distance of EA group were both significantly shortened (both P < 0.05), and the percentage of staying time in the target quadrant was significantly increased (P < 0.05). The immunohistochemical results showed that, compared with the control group, the positive expressions of SYN and PSD95 in the hippocampus of the model group were significantly down-regulated (both P < 0.05). Compared with the model group, the positive expressions of SYN and PSD95 in the hippocampus of the EA group were significantly up-regulated (both P < 0.05).Conclusions: EA in the treating principle of “soothing the liver and regulating the kidney” can effectively relieve anxiety-like behavior and improve spatial learning and memory ability of rats with PTSD, and the mechanism is related to the up-regulation of the expressions of SYN and PSD95 in the hippocampus.

The Effect of Electroacupuncture Preconditioning on Regional Cerebral Oxygen Saturation Levels in Elderly Patients with Diabetes.

ObjectiveThis study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes.MethodsForty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45–75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists’ physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared.ResultsThere was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001).ConclusionElectroacupuncture stimulation can increase rSO2 levels in patients with diabetes.Clinical Registration NumberChiCTR2100048783 (http://www.chictr.org.cn).