Low-frequency Electroacupuncture Research Articles

Map activation of various brain regions using different frequencies of electroacupuncture ST36, utilizing the FosCreER strategy

Objective: Electroacupuncture (EA) is an alternative treatment option for pain. Different frequencies of EA have different pain-relieving effects; however, the central mechanism is still not well understood. Methods: The Fos2A-iCreER (TRAP):Ai9 mice were divided into three groups (sham, 2 Hz, and 100 Hz). The mice were intraperitoneally injected with 4-hydroxytamoxifen (4-OHT) immediately after EA at Zusanli (ST36) for 30 min to record the activated neurons. One week later, the mice were sacrificed, and the number of TRAP-treated neurons activated by EA in the thalamus, amygdala, cortex, and hypothalamus was determined. Results: In the cortex, 2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1 (Cg1) and primary somatosensory cortex (S1), and 2 and 100 Hz EAs did not differ from sham EA. TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex (IC) and secondary somatosensory cortex (S2) compared with those activated by 100 Hz and sham EA. In the thalamus, the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus (PV) compared with those activated by sham EA. In the ventrolateral thalamic nucleus (VL), the number of TRAP-treated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA, and sham EA showed no difference compared with 2 or 100 Hz EA. TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus (VPL) by 2 Hz EA than by 100 Hz or sham EA. Conclusions: Low-frequency EA ST36 effectively activates neurons in the Cg1, S1, S2, IC, VPL, PV, and VL. The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

LIU Zhishun's clinical experience of electroacupuncture for pediatric neurogenic bladder of lower motor neuron type in children

Professor LIU Zhishun's clinical experience of electroacupuncture (EA) for pediatric neurogenic bladder of lower motor neuron type in children is summarized. Considering the unique physiological and pathological characteristics of children, with the strategy of combining "disease-symptom-location" in the selection of acupoints, professor LIU Zhishun proposes that the main disease location is the bladder and kidney, with the involvement of the conception vessel, governor vessel, kidney meridian of foot-shaoyin and the bladder meridian of foot-taiyang. The primary acupoint prescription-1 (bilateral Zhongliao [BL 33], Ciliao [BL 32] and Huiyang [BL 35]) and primary acupoint prescription-2 (Guanyuan [CV 4], Zhongji [CV 3] and bilateral Sanyinjiao [SP 6]) are selected to promote the yang of the governor vessel, stimulate the yin of the conception vessel, and invigorate the bladder's qi transformation. Before acupuncture, the four-step method is applied to precisely locate Ciliao (BL 32) and Zhongliao (BL 33). During acupuncture, the importance of achieving deqi is emphasized, with deep insertion in the sacral area to reach the disease location. Based on the tolerance characteristics of children, low-frequency EA and gentle moxibustion treatment are applied.

Low-frequency electroacupuncture exerts antinociceptive effects through activation of POMC neural circuit induced endorphinergic input to the periaqueductal gray from the arcuate nucleus.

It has been widely recognized that electroacupuncture (EA) inducing the release of β-endorphin represents a crucial mechanism of EA analgesia. The arcuate nucleus (ARC) in the hypothalamus is a vital component of the endogenous opioid peptide system. Serving as an integration center, the periaqueductal gray (PAG) receives neural fiber projections from the frontal cortex, insular cortex, and ARC. However, the specific mechanisms how EA facilitates the release of β-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and in vitro experiments by transcriptomics, microdialysis, photogenetics, chemical genetics, and calcium imaging, combined with transgenic animals. Firstly, we detected 2Hz EA at the Zusanli (ST36) increased the level of β-endorphin and transcriptional level of proopiomelanocortin (POMC). Our transcriptomics profiling demonstrated that 2Hz EA at the ST36 modulates the expression of c-Fos and Jun B in ARC brain nuclear cluster, and the transcriptional regulation of 2Hz EA mainly occur in POMC neurons by Immunofluorescence staining verification. Meaning while, 2Hz EA specifically activated the cAMP-PKA-CREB signaling pathway in ARC which mediating the c-Fos and Jun B transcription, and 2Hz EA analgesia is dependent on the activation of cAMP-PKA-CREB signaling pathway in ARC. In order to investigate how the β-endorphin produced in ARC transfer to integration center PAG, transneuronal tracing technology was used to observe the 2Hz EA promoted the neural projection from ARC to PAG compared to 100Hz EA and sham mice. Inhibited PAGGABA neurons, the transfer of β-endorphin from the ARC nucleus to the PAG nucleus through the ARCPOMC-PAGGABA neural circuit. Furthermore, by manipulating the excitability of POMC neurons from ARCPOMC to PAGGABA using inhibitory chemogenetics and optogenetics, we found that this inhibition significantly reduced transfer of β-endorphin from the ARC nucleus to the PAG nucleus and the effectiveness of 2Hz EA analgesia in neurological POMC cyclization recombination enzyme (Cre) mice and C57BL/6J mice, which indicates that the transfer of β-endorphin depends on the activation of POMC neurons prefect from ARCPOMC to PAGGABA. These findings contribute to our understanding of the neural circuitry underlying the EA pain-relieving effects and maybe provide valuable insights for optimizing EA stimulation parameters in clinical pain treatment using the in vivo dynamic visual investigating the central analgesic mechanism.

Electroacupuncture ameliorates hepatic defects in a rat model of polycystic ovary syndrome induced by letrozole and a high-fat diet.

This study was designed to evaluate the effects of low-frequency electroacupuncture (EA) on glucose and lipid disturbances in a rat model of polycystic ovary syndrome (PCOS) characterized by insulin resistance (IR) and hepatic steatosis. The PCOS rat model was induced by continuous administration of letrozole (LET) combined with a high-fat diet (HFD). Female Sprague-Dawley rats were divided into the following four groups: control, control + EA, LET + HFD and LET + HFD + EA. EA was administered five or six times a week with a maximum of 20 treatment sessions. Body weight, estrous cyclicity, hormonal status, glucose and insulin tolerance, lipid profiles, liver inflammation factors, liver morphology and changes in the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway were evaluated. The rat model presented anovulatory cycles, increased body weight, elevated testosterone, abnormal glucose and lipid metabolism, IR, liver inflammation, hepatic steatosis and dysregulation of the insulin-mediated PI3-K/Akt signaling axis. EA reduced fasting blood glucose, fasting insulin, area under the curve for glucose, homeostasis model assessment of IR indices, triglycerides and free fatty acids, and alleviated hepatic steatosis. Furthermore, low-frequency EA downregulated mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6, upregulated mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α, increased protein expression of phosphorylated (p)-Akt (Ser473), p-glycogen synthase kinase (GSK) 3β (Ser9) and glucose transporter 4 (GLUT4), increased the ratio of p-GSK3β to GSK3β and downregulated protein expression of GSK3β. An obese PCOS rat model with IR and hepatic steatosis was successfully established by the combination of LET and HFD. EA improved dysfunctional glucose and lipid metabolism in this PCOS-IR rat model, and the molecular mechanism appeared to involve regulation of the expression of key molecules of the PI3-K/Akt insulin signaling pathway in the liver.

A randomized controlled trial with a combination of low frequency electroacupuncture and cognitive behavioral therapy for short-term insomnia

ObjectiveTo explore the therapeutic effects of low frequency electroacupuncture (EA) combined with cognitive behavioral therapy (CBT) for short-term insomnia. MethodsPatients with “short-term insomnia” were randomly divided into the treatment and control groups. Patients in the treatment group were treated with low-frequency EA combined with CBT, while those in the control group were only treated with low-frequency EA. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) scores in the two groups were compared before and after treatment within the same group, as well as between the two groups. After four weeks of treatment, the comprehensive therapeutic effects of both treatment modalities and the number of people who developed chronic insomnia were compared. ResultsThe differences in PSQI score, PSQI sleep rate, ISI score, and DBAS score band after treatment, within the same group and between groups were statistically significant. There was significant difference in DBAS score between the two groups before and after treatment, and in the composition ratio of comprehensive therapeutic effects between the two groups. ConclusionLow-frequency EA combined with CBT and low-frequency EA alone can significantly improve sleep cycles in patients with insomnia, reduce the sleep severity index, prevent daytime sleepiness symptoms in patients, and improve cognition in patients. Low-frequency EA combined with CBT had better therapeutic effects and improved cognition in patients, and hence can be recommended.

Electroacupuncture relieves portal hypertension by improving vascular angiogenesis and linking gut microbiota in bile duct ligation rats.

The pathological increase in the intrahepatic resistance and decrease peripheral vascular tone in the development of portal hypertension (PHT). PHT has been linked to lower microbial diversity and weakened intestinal barrier, and interplay alters inflammatory signaling cascades. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study addresses the possible mechanisms underlying putative hemodynamics effects of EA in PHT rats. PHT was induced by bile duct ligation (BDL) over 7 days in rats. BDL rats were treated with low-frequency EA (2 Hz) at acupoint, ST36, 10 min once daily for 7 consecutive days. EA significantly reduced portal pressure and enhanced maximum contractile responses in the aorta, and blunts the angiogenesis cascade in PHT rats. EA decreased the aortic angiogenesis signaling cascade, reflected by downregulated of ICAM1, VCAM1, VEGFR1, and TGFβR2 levels. In addition, EA preserved claudin-1, occludin, and ZO-1 levels in BDL-induced PHT model. Furthermore, EA demonstrates to have a positive effect on the gut Bacteroidetes/Firmicutes ratio and to reduce pro-inflammatory cytokines and endotoxins. These results summarize the potential role of EA in the gut microbiota could potentially lead to attenuate intestine injury which could further contribute to vascular reactivity in PHT rats.

Efficacy of Low-Frequency Electroacupuncture on Urinary Retention After Spinal Anesthesia

PurposeThis study was designed to evaluate the efficacy of low-frequency electroacupuncture (EA) in the prevention of urinary retention after orthopedic surgery. DesignA double-blind placebo-controlled clinical trial. MethodsEighty patients with spinal anesthesia were randomly allocated into the groups of EA (40 cases) and control (40 cases). In the first group, the EA was applied to four points of SP6, SP9, ST28, and CV2; 4 Hz, retaining for 20 minutes in the postanesthesia care unit (PACU). In the control group, no intervention was applied. The incidence of postoperative urinary retention, incomplete or difficult urination, and the first automatic micturition time since spinal anesthesia were compared between the two groups. FindingsThe incidence of urinary retention and incomplete urination in the EA group was significantly lower than that in the control group; the time to first urination was shorter in the intervention group than in the control group (P < .05). ConclusionsElectroacupuncture after spinal anesthesia improves bladder function and reduces the need for a urinary catheter and its possible complications.

The effect of low-frequency electroacupuncture on hemodynamic parameters and nausea in cesarean section patients under spinal anesthesia

BackgroundHemodynamic changes and nausea remain common side effects of spinal anesthesia for parturients. It is suggested that electroacupuncture (EA) at master points of pericardial and heart meridians may have inotropic and vasoconstrictive effects. This study was conducted to evaluate the effects of low-frequency EA at the Neiguan (PC-6) and Shenmen (HE-7) points on the incidence of hypotension, bradycardia, and nausea in patients undergoing cesarean section under spinal anesthesia. MethodsIn a double-blind clinical trial, 90 otherwise healthy candidates for elective cesarean section under spinal anesthesia were enrolled. Patients were allocated to receive stimulation with a frequency of 2 Hz for 20 min at PC-6 and HE-7 points (EA group), stimulation at two non-acupoints of the shoulder, and no treatment (control). Serial measurements of blood pressure, heart rate (HR), and the incidence of nausea and vomiting were compared among the three groups. ResultsMore ephedrine was required to maintain arterial blood pressure in the control and non-acupoint groups compared with the acupoint group (53.3, 30.3, and 21%, respectively; p=0.05). The severity of nausea and occurrence of vomiting in the acupuncture group was significantly lower than in the other two groups (p=0.01). ConclusionLow-frequency EA at the PC-6 and HE-7 points reduces the incidence of hypotension and severity of nausea/vomiting in cesarean section patients under spinal anesthesia.

Effects of electroacupuncture on the kisspeptin-gonadotropin-releasing hormone (GnRH) /luteinizing hormone (LH) neural circuit abnormalities and androgen receptor expression of kisspeptin/neurokinin B/dynorphin neurons in PCOS rats

BackgroundPolycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Electroacupuncture (EA) can effectively improve hyperandrogenism and increase ovulation frequency in patients with PCOS. Pieces of suggest that androgen activity in the brain is associated with impaired steroid negative feedback in such patients. Studies have shown that EA regulated androgen receptor (AR) expression and local factor levels (such as anti-Müllerian hormone and inhibin B) in the ovary of PCOS rats. However, few studies have explored the effect of EA on androgen activity in the brain.ObjectiveThis study investigated the effect of EA on the kisspeptin-gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) neural circuit and sex hormone receptor expression in the hypothalamus of PCOS rats.MethodsPCOS signs were induced by letrozole administration, and the induced rats were treated with low-frequency EA at Guan Yuan acupoint (CV4). The effect of EA on PCOS-like signs was evaluated by observing changes in the body weight, ovarian quality, ovarian morphology, and serum sex hormone levels in rats. To explore the mechanism of the effect of EA on PCOS-like signs, the neuropeptide content of the kisspeptin-GnRH/LH neural circuit was assessed using enzyme-linked immunosorbent assay(ELISA); AR and estrogen receptor α (ERα) coexpression on kisspeptin/neurokinin B/dynorphin (KNDy) neurons was determined via triple-label immunofluorescence; and protein and mRNA expression of Kiss1, Ar, Esr1, and kisspeptin receptor (Kiss1r) was evaluated via western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR).ResultsThe results revealed that the estrous cycle of rats in the EA treatment group recovered, and their body and ovary weight reduced; ovarian morphology improved; serum testosterone and LH levels significantly decreased; and kisspeptin, GnRH, and dynorphin levels in hypothalamic arcuate nucleus significantly decreased. Compared with controls, the number of AR/Kiss1-positive cells increased, number of ERα/Kiss1-positive cells decreased, and protein and mRNA expression of Kiss1, Ar, and Kiss1r significantly increased in PCOS rats. However, EA treatment reversed these changes and reduced the expression of Kiss1, Ar, and Kiss1r significantly.ConclusionImprovement in the reproductive hallmarks of PCOS rats via EA may be achieved by regulating the kisspeptin-GnRH/LH circuit via androgen activity attenuation. Thus, the results provide an experimental basis for acupuncture as an adjuvant medical therapy on PCOS.

EEG and ECG Power Spectrum Analysis of Sedative Effects on Propofol-Anesthetized Rats with Electroacupuncture.

Background In previous studies, electroacupuncture (EA) with 2/15 Hz has been shown to enhance the sedative effects in general anesthesia patients. Central lateral thalamic stimulation of 50 Hz showed an arousal effect in macaques. Therefore, it is worth studying the sedative effect of EA at peripheral acupoints with different frequencies, especially the frequency of around 50 Hz. Methods Rats were anesthetized under the constant infusion of propofol and EA at Zusanli (ST36) and Neiguan (PC6) locations. Electroencephalography (EEG) and heart rate were continuously recorded before and after the intervention by EA in the C group (control), LEA group (low-frequency group, 2/15 Hz diffuse/dense wave EA stimulation), and HEA group (high-frequency group, 50 Hz stimulation). Results In the LEA group, a significant increase in the power of the delta component with a decrease in the alpha component (p < 0.05) was observed after EA stimulation. In the HEA group, significant increases in the powers of alpha and beta components of EEG (p < 0.05) and a decrease in the delta component of EEG were observed (p < 0.05). The phenomenon is also shown in full-frequency waves. In addition, a significant decrease in the low-frequency/high-frequency ratio parameter was observed in the LEA group. Conclusions EA at bilateral ST36 and PC6 can enhance the sedative effects of propofol anesthesia in low-frequency stimulation but lighten the sedative effects in high-frequency (50 Hz) stimulation. The sympathetic-vagal balance was affected due to low-frequency EA.

Electroacupuncture improves endometrial receptivity through miRNA-223-3p-mediated regulation of leukemia inhibitory factor / signal transducer and activator of transcription 3 signaling pathway

ABSTRACT Ovulation-inducing drugs such as endogenous steroids could reduce endometrial receptivity during the implantation window, resulting in lower clinical pregnancy rates and higher miscarriage rates. The present study employed electroacupuncture therapy along with different frequencies on elevating impaired endometrial receptivity to elucidate the mechanism therein. The rats were split up into seven groups of normal, model, low-frequency electroacupuncture (LF-EA), high-frequency electroacupuncture (HF-EA), LF-EA+anti-miRNA, HF-EA+anti-miRNA, and anti-miRNA. PCR assays were used to detect miR-223-3p expressions. The effects of electroacupuncture and miR-223-3p on rats’ endometrial membrane cell-drinking process in a manner of scanning electron microscopy were recorded. After that we observed on the electroacupuncture effects on the conditions of adhesion molecules and LIF/STAT3 signaling pathway with assays of immunofluorescence and Western Blot. This study was end up with dual luciferase assay, where combination of miR-233-3p onto the 3’-UTR sequence of LIF was determined. PCR assay demonstrated that HF-EA procured an inhibition in miR-223-3p expression, whereas scanning electron microscopy turned out that both electroacupuncture and miR-223-3p were capable of raising the amount of intrauterine pinocytosis and the number of blastocyst implantation in rats. Additionally, assays of Western Blot and immunofluorescence showed that therapy of electroacupuncture brought about decreasing expressions in adhesion molecules of E-cadherin, β-catenin and claudin-1 (CLDN1). We found that both electroacupuncture and miR-223-3p were able to fortify LIF/STAT3 signaling pathway, then the fact of miR-223-3p combination to LIF 3’-UTR sequence was validated via our dual-luciferase assay. Electroacupuncture therapy inhibited the miR-223-3p expression upon LIF/STAT3 signaling pathway to elevate endometrial receptivity.

Low-frequency electroacupuncture improves disordered hepatic energy metabolism in insulin-resistant Zucker diabetic fatty rats via the AMPK/mTORC1/p70S6K signaling pathway.

Disordered hepatic energy metabolism is found in obese rats with insulin resistance (IR). There are insufficient experimental studies of electroacupuncture (EA) for IR and type 2 diabetes mellitus (T2DM). The aim of this study was to probe the effect of EA on disordered hepatic energy metabolism and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase, 70-kDa (p70S6K) signaling pathway. Zucker Diabetic Fatty (ZDF) rats were randomly divided into three groups: EA group receiving EA treatment; Pi group receiving pioglitazone gavage; and ZF group remaining untreated (n = 8 per group). Inbred non-insulin-resistant Zucker lean rats formed an (untreated) healthy control group (ZL, n = 8). Fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were measured. Hematoxylin-eosin (H&E) staining was used to investigate the liver morphologically. The mitochondrial structure of hepatocytes was observed by transmission electron microscopy (TEM). Western blotting was adopted to determine protein expression of insulin receptor substrate 1 (IRS-1), mTOR, mTORC1, AMPK, tuberous sclerosis 2 (TSC2) and p70S6K, and their phosphorylation. RT-PCR was used to quantify IRS-1, mTOR, mTORC1, AMPK and p70S6K mRNA levels. Compared with the ZF group, FPG, FINS, C-peptide, CRP and HOMA-IR levels were significantly reduced in the EA group (p < 0.05, p < 0.01). Evaluation of histopathology showed improvement in liver appearances following EA. Phosphorylation levels of AMPK, mTOR and TSC2 decreased, and IRS-1 and p70S6K increased, in hepatocytes of the ZF group, while these negative effects appeared to be alleviated by EA. EA can effectively ameliorate IR and regulate energy metabolism in the ZDF rat model. AMPK/mTORC1/p70S6K and related molecules may represent a potential mechanism of action underlying these effects.

High-frequency electroacupuncture improves endometrial receptivity via regulating cell adhesion molecules and leukemia inhibitory factor / signal transducer and activator of transcription signaling pathway

ABSTRACT Controlled ovarian hyperstimulation (COH) impairs the endometrium receptivity during the implantation window, resulting in a lower clinical pregnancy rate and a higher abortion rate. Our study explored the effect of electroacupuncture on the endometrial receptivity of COH rats. Female rats were randomly divided into normal treatment (Normal), model treatment (Model), low-frequency electroacupuncture treatment (LF-EA) and high-frequency electroacupuncture treatment (HF-EA). Rats in the Model, LF-EA, and HF-EA treatment groups were injected with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) to establish a model of COH rats. Compared with the Normal, the endometrial thickness, the number of pinopodes and amount of blastocyst implantation in the Model group were significantly reduced. Among them, the endometrial thickness and the amount of blastocyst implantation in the Model group were substantially decreased than those in the HF-EA group. High-frequency electroacupuncture treatment could markedly reduce the protein expression levels of E-cadherin, β-catenin and claudin-1 (CLDN1). During HF-EA treatment, the LIF/STAT3 signaling pathway of COH rats was enhanced. In conclusion, electroacupuncture could improve the endometrium receptivity and promote the blastocyst implantation in COH rats by reducing cell adhesion molecules and enhancing the LIF/STAT3 signaling pathway. Highlights High-frequency electroacupuncture could effectively improve endometrial receptivity and blastocyst implantation amount in COH rats. Electroacupuncture, especially high-frequency electroacupuncture, could significantly increase endometrial thickness and the number of pinopodes. High-frequency electroacupuncture significantly reduced the protein expression levels of E-cadherin, β-catenin and CLDN1 adhesion molecules in COH rats. High-frequency electroacupuncture could markedly enhance the LIF/STAT3 signaling pathway in COH rats.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation.

A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

Impact of Low Frequency Electro-acupuncture on Glucose and Lipid Metabolism in Unmarried PCOS Women: A Randomized Controlled Trial.

To explore the effect of electro-acupuncture (EA) on glucose and lipid metabolism in unmarried patients with polycystic ovary syndrome (PCOS). Fifty-four PCOS patients were equally randomized into true acupuncture group and sham acupuncture group (control) for totally 16 weeks of treatment by random method with a computerized randomization program. Patients in true acupuncture group accepted traditional acupuncture methods with EA and two sets of acupoint groups were used alternatively. The first set consisted of Zhongji (CV 3), Qihai (CV 6), Guilai (ST 29), Sanyinjiao (SP 6), Yinlingquan (SP 9), Hegu (LI4) and Baihui (GV 20), and the second set consisted of Tianshu (ST 25), ST 29, CV 3, CV 6, SP 6, Taichong (LR 3), Neiguan (PC) 6 and GV 20. Patients in the sham acupuncture group accepted shallow acupuncture methods through EA without electricity at 4 non-meridian points in each shoulder and upper arm. Outcome measures included body mass index (BMI), waist-hip-ratio (WHR), oral glucose tolerance test (OGTT), insulin release test, glucose and lipid metabolism indicators such as total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, adiponectin, leptin, visfatin, resistin, and interleukin (IL-6). Twenty-six subjects in the true acupuncture group and 20 subjects in the sham group completed the clinical trial. After 16 weeks of treatment, no significant difference in the outcome measures were observed between the two groups (P>0.05). However, as compared with baseline data, a reduction in weight, BMI, hipline, WHR, fasting glucose, homeostatic model assessment of insulin sensitivity, visfatin and HDL-C, and an increase in resistin and IL-6 were observed in the true acupuncture group (P<0.05). In addition, a reduction in visfatin and an increase in TC were also observed in the sham group (P<0.05). Acupuncture may have a beneficial effect in the treatment of PCOS by improving glucose and lipid metabolism. Moreover, the sham acupuncture may be not completely ineffective. Sham acupuncture may improve some of the aspects of the glucose and lipid metabolism of PCOS patients through a placebo effect. (Registration Nos. ChiCTR-TRC-12002529 and NCT01812161).

Electroacupuncture facilitates M2 macrophage polarization and its potential role in the regulation of inflammatory response

The underlying mechanism of electroacupuncture (EA) in relieving obesity, anti-inflammation and the interaction with metabolic pathways in obese mice has not been elaborated. The aim of this study was to investigate the regulation of EA on macrophage polarization in obesity tissue of diet-induced obesity mice. Mice were divided in 6 groups: normal control group, model group, EA-7 group, EA-14 group, EA-21 group and EA-28 group. Low-frequency EA was applied at “Tianshu (ST 25)”, “Guanyuan (CV 4)”, “Zusanli (ST 36)” and “Sanyinjiao (SP 6)” for 10 min. Adipose tissue was assessed with hematoxylin and eosin staining. Adipocytokines and pro-inflammatory factors expression was measured by ELISA. The protein and mRNA levels of macrophage markers were examined by immumohistochemical staining and RT-PCR, respectively. EA treatment was associated with a decrease of adipose tissue and large adipocytes, and an increase of small adipocytes. After EA treatment, the levels of Leptin, Chemerin, TNF-α, F4/80, iNOS, and CD11c decreased obviously in adipose tissue, while IL-4, IL-10 and CD206 levels increased significantly. Besides, TNF-α in spleen tissue was also downregulated, but IL-4 and IL-10 were upregulated. EA prevents weight gain through modulation inflammatory response and macrophage polarization in obese adipose tissues.

Clinical observation of electroacupuncture with different frequencies for migraine without aura

To observe the clinical efficacy of electroacupuncture (EA) with different frequencies in treating migraine. Ninety patients with migraine were divided into a low frequency electroacupuncture (LF-EA) group, a high frequency electroacupuncture (HF-EA) group and a variable frequency electroacupuncture (VF-EA) group by the random number table method. Shuaigu (GB 8), Hegu (LI 4), Waiguan (TE 5), Taichong (LR 3), Taiyang (EX-HN 5), Fengchi (GB 20) and Ashi points were selected for all three groups. After achieving needling sensation (Deqi), the LF-EA group received 2 Hz continuous wave EA stimulation; the HF-EA group received 100 Hz continuous wave EA stimulation, and the VF-EA group received 2 Hz/100 Hz sparse-dense wave EA stimulation. The EA stimulation lasted for 30 min in all the three groups, once a day, 10 times as a course, and the clinical efficacy was evaluated after 2 consecutive courses of treatment. After treatment, the total effective rates in the LF-EA group, HF-EA group and VF-EA group were 77.7%, 83.3% and 93.3%, respectively. The difference in total effective rate between the LF-EA and HF-EA groups was not statistically significant (P>0.05), but the total effective rate was significantly higher in the VF-EA group than in the LF-EA and HF-EA groups (both P 0.05), while the score was significantly lower in the VF-EA group than in the LF-EA and HF-EA groups (both P<0.01). VF-EA (2 Hz/100 Hz), compared with LF-EA (2 Hz) and HF-EA (100 Hz), shows superior clinical efficacy in treating migraine.

Electroacupuncture Regularizes Gastric Contraction and Reduces Apoptosis of Interstitial Cells of Cajal in Diabetic Rats.

Background/AimsGastric dysmotility is a frequent complication among patients with diabetes mellitus. Electroacupuncture (EA) has been empirically used to relieve gastrointestinal symptoms. The aims of this study were to investigate the effects of EA on gastric contraction and the mechanisms of interstitial cells of Cajal (ICC) involved.Materials and MethodsMale Sprague–Dawley rats were randomized into the normal control, diabetes (DM), diabetic and sham EA (DM + SEA), diabetic and low-frequency EA (DM + LEA), and diabetic and high-frequency EA (DM + HEA) groups. Diabetic models were established and then treated with EA for 8 weeks. Body weight and blood glucose were recorded every 2 weeks. The spontaneous contractions of distal gastric strips were analyzed. Immunostaining and RT-PCR were used to test the apoptotic ICC, IGF-1/IGF-1R, and Nrf2/HO-1 pathways.ResultsThe body weight in the DM + LEA and DM + HEA groups were increased compared with that of the DM group, though there was no effect on the blood glucose. The gastric contractions were obviously disordered in the DM group, but EA could regularize the contractions. The number of apoptotic ICC was dramatically increased in the DM group, but reduced with EA treatment. Meanwhile, the IGF-1/IGF-1R pathway was verified to be significantly altered in diabetic rats. The Nrf2/HO-1 pathway was not significantly increased in the DM group. EA with different frequencies efficiently improved the expression of IGF-1/IGF-1R signaling and activated the Nrf2/HO-1 pathway.ConclusionEA could improve gastric motility dysfunction and attenuate ICC apoptosis possibly through the regulation of IGF-1/IGF-1R and Nrf2/HO-1 pathways. EA may be a potential therapeutic method for diabetic gastric motility dysfunction.

Effect of electroacupuncture combined with aerobic exercise on IGF-I /Akt pathway in skeletal muscle of aging rats

To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein. Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot. In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (P<0.05). (2) Compared with YC group, the increase of the expression of IGF-I mRNA in YEA group was more obvious(P=0.051). (3)The expression of p-Akt and p-mTOR in YA group was significantly higher than that in YC group (P<0.05), and the expressionof p-mTOR, p-p70S6K also showed an increasing trend in YEA group (P>0.05). Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.

Electroacupuncture accelerates the delayed intestinal transit in POI by suppressing M1 like muscularis macrophages and IL6 secretion.

Electroacupuncture (EA) at ST-36 could accelerate the delayed gastrointestinal (GI) motility in many GI motility dysfunction models, but the definite effect and mechanisms are unclear. In this study, we intended to investigate the effects of EA on intestinal manipulation (IM) mice model and involved mechanisms. Male C57BL/6 mice were randomized into five groups: normal control, intestinal manipulation (IM), IM with sham EA (SEA), IM with high-frequency EA (HEA), and IM with low-frequency EA (LEA). The GI transit was evaluated. The infiltration of muscularis macrophages (MMφ) and its phenotype were analyzed with flow cytometry. Magnetic-activated cell sorting was applied to isolate MMφ, and the relationship between the MMφ and interstitial cells of Cajal (ICCs) was further investigated. (1) Compared with the IM group, HEA and LEA attenuated the delayed intestinal transit. (2) Both the HEA and LEA obviously reduced the MMφ and suppressed the M1 activation of the MMφ in the ileum. (3) EA restored the disrupted ICC networks through inhibiting the release of IL6 by the MMφ. (1) Electroacupuncture at acupoint ST-36 could accelerate the delayed intestinal transit in the IM murine model by restoring the ICC networks. (2) EA protected the ICCs through reducing the MMφ, inhibiting its M1 polarization and its IL6 secretion.