Protective Effect Of Shenfu Injection Research Articles

Protective Effect of Shenfu Injection against Sepsis-induced Acute Lung Injury by Suppressing Inflammation and Apoptosis Through the Regulation of the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway

Abstract Objective: Sepsis-induced acute lung injury (ALI) is a clinically critical condition with a high mortality rate. Shenfu injection (SFI) is a Chinese herbal medicine extracted from red ginseng and Aconite, Radix Aconiti, with various pharmacological activities. This study aimed to investigate the potential mechanism of action of SFI in preventing sepsis-induced ALI. Materials and Methods: We established a mouse model of sepsis-induced ALI by cecal ligation and puncture (CLP). The mice were randomly divided into three groups (n = 8): Sham, CLP, and SFI (10 mL/kg). Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for pathological analysis, enzyme-linked immunosorbent assay, immunohistochemistry (IHC), and protein detection. Results: Our results showed that SFI significantly ameliorated pathological damage caused by CLP-induced ALI. SFI treatment significantly decreased the lung wet-to-dry weight ratio. In addition, SFI treatment significantly reduced the protein levels and cell numbers in the BALF. SFI could significantly reduce the levels of tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1β in plasma and BALF. SFI significantly reduced the protein expression of Bax and cleaved caspase-3 and increased the protein levels of Bcl-2. Western blotting and IHC results showed that SFI reduced the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Conclusions: In a septic ALI mouse model, SFI inhibited apoptosis and inflammation through the JAK2/STAT3 pathway, providing a candidate drug for the treatment of septic ALI.

Shenfu injection targets the PI3K-AKT pathway to regulate autophagy and apoptosis in acute respiratory distress syndrome caused by sepsis

BackgroundSepsis is a life-threatening organ dysfunction caused by an exaggerated response to infection. In the lungs, one of the most susceptible organs, this can manifest as acute respiratory distress syndrome (ARDS). Shenfu (SF) injection is a prominent traditional Chinese medicine used to treat sepsis. However, the exact mechanism of its action has rarely been reported in the literature. PurposeIn the present study, we detected the protective effect of SF injection on sepsis-induced ARDS and explored its underlying mechanism. MethodsWe investigated the potential targets and regulatory mechanisms of SF injections using a combination of network pharmacology and RNA sequencing. This study was conducted both in vivo and in vitro using a mouse model of ARDS and lipopolysaccharide (LPS)-stimulated MLE-12 cells, respectively. ResultsThe results showed that SF injection could effectively inhibit inflammation, oxidative stress, and apoptosis to alleviate LPS-induced ARDS. SF inhibited the PI3K-AKT pathway, which controls autophagy and apoptosis. Subsequently, MLE-12 cells were treated with 3-methyladenine to assess its effects on autophagy and apoptosis. Additional experiments were conducted by adding rapamycin, an mTOR antagonist, or SC79, an AKT agonist, to investigate the effects of SF injection on autophagy, apoptosis, and the PI3K-AKT pathway. ConclusionOverall, we found that SF administration could enhance autophagic activity, reduce apoptosis, suppress inflammatory responses and oxidative stress, and inhibit the PI3K-AKT pathway, thus ameliorating sepsis-induced ARDS.

Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

Protective effect of Shenfu Injection on rats with chronic heart failure based on HMGB1/TLR4/NF-κB signaling pathway

The study aimed to explore the mechanism and targets of Shenfu Injection in the regulation of inflammatory injury in chronic heart failure rats based on the high mobility group box-1/Toll like receptor 4/nuclear factor kappa-B(HMGB1/TLR4/NF-κB) signaling pathway. The rat model of chronic heart failure was established using isoproterenol. The modeled rats were divided into three groups by random number table: the model group, Shenfu group and glycopyrrolate group, and the normal group was also set. The rats were administrated for 15 consecutive days, and on the following day after the last administration, they were sacrificed for sample collection. The cardiac mass index and left ventricular mass index of the rats in each group were measured, and the echocardiogram was used to analyze the cardiac function indices, and ELISA to test the inflammatory indices in rat serum. The pathological morphology and fibrosis status of rat heart tissues were observed by HE staining and Masson staining, respectively. The content of HMGB1 was determined by immunofluorescence staining. The protein and mRNA expression of HMGB1/TLR4/TLR4 signaling pathway was detected by Western blot and RT-qPCR, respectively. The results showed that the chronic heart failure rat model was successfully prepared. The rats in the model group had reduced cardiac function, increased levels of HMGB1 and inflammatory factors(P<0.05), and elevated protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), with fibrous connective tissue hyperplasia, inflammatory cell infiltration and severe fibrosis. Shenfu Injection improved cardiac function, decreased the levels of HMGB1 and inflammatory factors(P<0.05) and the protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), ameliorated interstitial fibrous connective tissue hyperplasia and inflammatory cell infiltration, and reduced fibrosis. In conclusion, Shenfu Injection can reduce inflammatory damage and improve cardiac function in chronic heart failure rats by regulating the HMGB1/TLR4/NF-κB signaling pathway.

Protective Effect of Shenfu Injection on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock.

To investigate the effects of Shenfu Injection (, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation.

Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5mL/kg in the SFI group; 15mg/kg nicorandil in the A2R agonist group; and 5mL/kg SFI plus 5mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Protective effect of Shenfu injection on the endothelium of severe sepsis by inhibiting CD11b+ cell paralysis induced by high mobility group protein B1

To investigate the relationship between the biochemical parameters, the pulmonary pathologic injury and the immune mechanism of severe sepsis in infant porcine, and the intervention effect of Shenfu injection. Panamanian infant porcine (2-3 months old) were divided into sham operation group (Sham group; intravenous injection of normal saline), lipopolysaccharide (LPS) induced severe sepsis model group (LPS group; intravenous injection of LPS 1 mg/kg, and continuing at 0.5 mg×kg-1×h-1 for 12 hours), and Shenfu injection intervention group (SF group; intravenous injection of Shenfu injection 10 mL/kg at the same time of modeling, twice a day) according to the random number table method, with 5 in each group. Forty-eight hours after the challenge, the changes of C-reactive protein (CRP), procalcitonin (PCT), oxygenation index (PaO2/FiO2), base excess (BE), blood lactate (Lac) and other biochemical indexes were detected with blood sampling; the number of neutrophils [myeloperoxidase positive (MPO+)] and their activated subsets CD11b+CD64+, M1 macrophages (CD80+CD64+), CD4+ and CD8+ T cells were analyzed in peripheral blood by flow cytometry. The levels of plasma cytokines were detected by enzyme linked immunosorbent assay (ELISA). The pathological damage of lung tissue was observed by hematoxylin-eosin (HE) staining. The mRNA expression of lung injury related molecules and their receptors, chemokines, cytokines, vascular endothelial related molecules and tight junction protein were detected by reverse transcription-polymerase chain reaction (RT-PCR). Compared with Sham group, the levels of CRP, PCT and Lac in LPS group significantly increased, and PaO2/FiO2 and BE significantly decreased. In the peripheral blood, CD80+CD64+ macrophages, CD11b+CD64+ and MPO+ neutrophils, CD4+, CD8+ T cells and tumor necrosis factor-α (TNF-α) significantly decreased, but interleukin-10 (IL-10) and vascular endothelial cell growth factor (VEGF) significantly increased; the mRNA expressions of high mobility group protein B1 (HMGB1), receptor for advanced glycation end products (RAGE), angiopoietin 2/angiopoietin 1 (Ang2/Ang1) significantly increased, Toll like receptor 9 (TLR9), chemokines (CXCL9 and CXCL10), TNF-α, IL-27, Tek tyrosine kinase 2 (TIE2), vascular endothelial cadherin (VE-CAD) and Occludin significantly decreased in lung tissue. HE staining showed inflammatory cell infiltration and exudation in the alveolar cavity, alveoli consolidation, thickening of the alveolar interstitial layer and emphysema. Compared with LPS group, Lac in SF group significantly decreased (mmol/L: 4.2±1.0 vs. 6.3±1.1, P < 0.05), while BE and PaO2/FiO2 significantly increased [BE (mmol/L): -6.4±2.6 vs. -11.6±2.5, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 180±36 vs. 105±35, both P < 0.05]; the percentage of CD80+CD64+ macrophages, CD11b+CD64+ and MPO+ neutrophils significantly increased [CD80+CD64+: (7.13±2.01)% vs. (3.80±0.46)%, CD11b+CD64+: (8.33±2.55)% vs. (2.15±0.47)%, MPO+: (21.22±2.33)% vs. (8.31±0.46)%, all P < 0.05]; the mRNA expressions of HMGB1 and RAGE decreased to some extent [HMGB1 mRNA (2-ΔΔCT): 1.81±0.45 vs. 2.23±0.85, RAGE mRNA (2-ΔΔCT): 6.69±3.48 vs. 11.60±6.91, both P < 0.05], the mRNA expressions of CXCL9 and TIE2 increased to a certain extent [CXCL9 mRNA (2-ΔΔCT): 1.06±0.63 vs. 0.50±0.12, TIE2 mRNA (2-ΔΔCT): 1.42±0.68 vs. 0.27±0.16, both P < 0.05]; the pathological damage of lung tissue were significantly alleviated. The increased abnormality of BE, Lac, and PaO2/FiO2, the immune exhausting and paralysis may be important factors leading to the fatal lung injury in infant porcine with severe sepsis. The possible mechanism is that the excessive activation of HMGB1 and its receptor RAGE, the suppression of TLR9 and corresponding chemokine and inflammatory factors lead to increased endothelial damage and decreased tight connection, which in turn induces capillary leakage. The intervention of immune disorders by Shenfu injection in the severe pneumonia accompanied by sepsis may be related to elevated M1 macrophages and activated neutrophils in the peripheral blood, inhibition of HMGB1 and its receptor RAGE mRNA expression, and elevated CXCL9 and TIE2 expression.

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

Objective To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. Methods Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. Results After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. Conclusion SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

The aim of present study was to assess the protective effects of Shenfu injection (SI) on the intestinal mucosa and its regulation on the mucosal immune responses in rats with sepsis. Sprague-Dawley rats were randomly divided into the sham, model, low-dose SI (LSF), and high-dose SI (HSF) groups. Sham animals underwent laparotomy only, whereas sepsis was modeled by cecal ligation and puncture in the remaining groups. At 2 h post-surgery, the LSF and HSF groups were intraperitoneally administered 5 and 20 mL/kg SI, respectively, whereas other animals with saline. At 12 h and 24 h post-surgery, eight rats per group were sacrificed, and blood and intestinal tissues were collected. The intestinal mucosa was analyzed by hematoxylin and eosin staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations, as well as secretory immunoglobulin A (sIgA) content in the intestinal mucosa, were evaluated by enzyme-linked immunosorbent assay. CD3 and γδT lymphocytes were quantified by flow cytometry. Animal survival until 72 h was also recorded. Intestinal mucosal injury was significantly higher in model animals than in sham animals at postoperative 12 h and 24 h. Serum TNF-α and IL-6 levels were markedly increased, whereas sIgA and CD3 and γδT cell amounts were overtly decreased (p<0.01). The LSF and HSF rats showed lower mortality, intestinal mucosal injury, and serum TNF-α and IL-6 levels (p<0.05), as well as higher sIgA levels and CD3 and γδT cell amounts, than the model group (p<0.01), with a dose-dependent manner. SI dose-dependently prolongs survival and protects the intestinal mucosa in rats with sepsis, possibly through strengthening innate immunity instead of acquired immunity.

Protective effects of shenfu injection on cerebral ischemia reperfusion injury in rats

Objective To study the protective effect of shenfu injection on cerebral ischemia reperfusion injury in rats. Methods 120 male Sprague Dawley (SD) rats(320-350 g) were randomly divided into sham operation group, model control group, Nimodipine injection group, low, medium and high dose group of shenfu injection according to gender weight. 20 males in each group were given medicine once a day for 7 days before operation. The cerebral ischemia model was established by thread embolization after 5 days of administration. In the sham operation group, the other operations were the same as those in the model group except for carotid artery ligation and thread insertion. After 24 hours of perfusion, the neurological score, abdominal aorta blood flow, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GHS) levels in brain tissues were measured. Triphenyltetrazolium chloride (TTC) staining was used to calculate the area of cerebral infarction and pathological examination of brain tissues. Results Compared with the model control group, the middle and high dosage of shenfu injection could obviously improve the nerve function and increase the percentage of cerebral infarction area (P<0.05); the high dosage group of shenfu injection could obviously decrease the whole blood viscosity (P<0.01); the middle and high dosage of shenfu injection could obviously reduce the level of MDA in rat brain tissue (P<0.01) while increasing the levels of SOD and GSH (P<0.01), finally could significantly improve the pathological changes of brain issues such as mild swelling of nerve fibers, mild neuronal degeneration, inflammatory interstitial edema and inflammation. Conclusions Shenfu injection has obvious protective effect on cerebral ischemia reperfusion model in rats. Key words: SHENFU DECOCTION/TU; Ischemic preconditioning; Brain ischemia; Reperfusion injury/DT; Rats

Protective Effects of Shenfu Injection against Myocardial Ischemia–Reperfusion Injury &lt;i&gt;via&lt;/i&gt; Activation of eNOS in Rats

The aim of the present study was to investigate the protective effects of Shenfu injection (SFI) against myocardial ischemia-reperfusion injury (MIRI) in model rats and to explore its mechanism of action. Sprague-Dawley (SD) rats were pretreated with SFI and NG-nitro-L-arginine methyl ester (L-NAME) via tail vein injection and then rats were subjected to ischemia by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Left ventricular function was evaluated by echocardiography. Hemodynamic was measured by the Millar pressure-volume system; serum creatine kinase (CK), lactate dehydrogenase (LDH) and serum troponin (TNNI3) levels were determined. Myocardial infarct size was observed by 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining; p-Akt/Akt, and p-endothelial nitric oxide synthase (p-eNOS)/eNOS levels were assessed by Western blotting; nitric oxide (NO) content in serum was determined by the Griess reaction. SFI significantly decreased serum CK, LDH and TNNI3 levels in MIRI rats, while it significantly increased the level of left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), maximal rate of the increase of left ventricular pressure (+dp/dtmax), maximal rate of the decrease of left ventricular pressure (-dp/dtmax), left ventricle ejection fraction percentage (EF), and stroke volume (SV). In addition, SFI significantly reduced myocardial infarction area and activated the phosphorylation of eNOS via Akt. The phosphorylation of eNOS and the concurrent increase of NO production contributed significantly to the protective effects of SFI. These results demonstrate that SFI protects the rat heart against MIRI and that this effect is mediated in part by Akt/eNOS signaling.

Protective effect of Shenfu injection preconditioning on lung ischemia-reperfusion injury.

Lung ischemia-reperfusion injury remains a problem in thoracic surgery, as minimal progress has been made concerning its prevention and control. In the present study, the protective effects and the underlying mechanism of Shenfu injection preconditioning on a rat lung ischemia-reperfusion model was investigated. Shenfu injection is a well-known Chinese traditional medicine, which is composed of Red Radix Ginseng and Radix Aconitum carmichaelii, with ginseng saponin and aconitum alkaloids as the active ingredients. A total of 72 specific pathogen-free, healthy male Wistar rats were randomly divided into control, model and Shenfu injection (10 ml/kg injection prior to injury) groups and were assessed at the following points: Ischemia 45 min; reperfusion 60 min; and reperfusion 120 min. Blood collected from the aorta abdominalis was cryopreserved at −70°C for the analysis of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. Lung tissues were divided into three equal sections in order to assess the wet-to-dry (W/D) lung ratio, tumor necrosis factor (TNF)-α expression levels, myeloperoxidase (MPO) activity, alveolar damage, total protein and hematoxylin and eosin staining. The results demonstrated that the lung W/D weight ratio, TNF-α expression levels and SOD activity in the Shenfu group were significantly lower at 120 min reperfusion (P<0.05), as compared with the model group. MPO and MDA activity significantly decreased following reperfusion at 60 and 120 min (P<0.05), as compared with the model group. In addition, the degree of alveolar damage in the Shenfu group was significantly decreased (P<0.05), as compared with the model group. In addition, compared with the model group, the degree of alveolar damage in the Shenfu group was significantly lower (P<0.05); however, no significant changes in total protein were observed. The extent of alveolar structural damage and the proportion of interstitial neutrophils and alveolar and interstitial red blood cells were lower in the Shenfu group, as compared with the model and control groups. Therefore, the results of the present study suggested that Shenfu injection may have protective effects on lung ischemia-reperfusion injury.

The protective effect of Shenfu injection against elderly severe pneumonia.

The purpose of this study is to investigate the effect of Shenfu injection (SFI) on the tumor necrosis factor-α (TNF-α) and the interleukin (IL-6, IL-8, IL-10) of elderly patients who suffered from severe pneumonia. From June 2012 to September 2014, we performed in our department 89 cases of elderly patients with severe pneumonia. These patients were randomly divided into two groups: the treatment group (45 cases) and the control group (44 cases). The control group was given the treatment of anti-infection, reducing sputum, and support therapy, while the treatment group was fed by SFI intravenously based on the control group. The TNF-α and the interleukin were detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the changes in the inflammatory response indicators, the blood gas analysis, and the parameters of vital signs were measured and compared before and after therapy. Prior to treatment, there is no significant difference between the treatment group and the control group (p>0.05); after the treatment for 7days, the levels of TNF-α, IL-6, and IL-8 were significantly decreased, while the level of IL-10 was obviously increased. The APACHE II score was significantly decreased in comparison to that before the treatment (p<0.05), and the time of mechanical ventilation, the duration of time in ICU, and the application time of vasoactive drugs were notably shortened. The application of Shenfu injection exhibited a positive and effective effect on removing the inflammation media during the treatment of elderly severe pneumonia.

The protective effects of Shen-Fu injection on experimental acute pancreatitis in a rat model.

Objectives. In the present study, we investigated the protective effects of Shen-Fu injection (SFI) on a caerulein-induced rat pancreatitis (AP) model. Methods. SFI was given to rats in the SFI treated group through intraperitoneal injection. Blood and pancreas samples were collected for serological and histopathological studies. Results. Our results showed that AP caused significant decrease in tissue glutathione (GSH) and serum IL-4 and IL-10, while pancreatic malondialdehyde (MDA) and myeloperoxidase (MPO) were increased. Furthermore, TNF-α, IL-1β, amylase, and lipase levels were also significantly increased. On the other hand, SFI treatment reserved all these biochemical indices as well as histopathologic alterations that were induced by caerulein. Conclusion. Our findings suggest that the SFI protects against caerulein-induced AP in rats via modulation of cytokines, oxidative stress, and Nuclear Factor-kappa B (NF-κB) activity.

Cardioprotection of Shenfu Injection (参附注射液) against myocardial ischemia/reperfusion injury in open heart surgery

To investigate the protective effect of Shenfu Injection (SFI) against myocardium ischemia/reperfusion injury (IRI) in mitral valve replacement (MVR) with cardiopulmonary bypass (CPB). Forty patients undergoing selective MVR were randomly assigned to the control group and trial Groups I, II, III, and IV according to the different administrations of SFI, 8 patients in each group. The changes of systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) in each group were monitored, respectively. The recovering percentage of spontaneous heart beat, the heart rate (HR) and cardiac rhythm as well as the abnormal duration of ECG-ST segment were recorded after the restoration of heart beat. The serum concentration of cardiac troponin I (cTnI), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were determined as well. (1) The SBP, MBP and DBP values, the recovering rate of spontaneous heart beat, HR, ECG-ST, atrioventricular block and ventricular arrhythmia were significantly improved in group IV compared with any other groups. (2) Compared with the control group, the postoperative serum contents of cTnI and MDA were significantly decreased, but the activity of SOD was significantly increased in group IV. SFI had a certain protective effect against myocardium IRI. Moreover, better efficacy was seen with the administration of 1.5 mL/kg SFI into CPB priming fluid and pumping 1.5 mL/kg SFI via CPB as soon as the clamped aorta was unclamped.

Myocardial protective effect of Shenfu injection in patients undergoing valve replacement

To investigate the myocardial protective effect of Shenfu injection in patients undergoing valve replacement. Forty patients undergoing valve replacement surgery under cardio-pulmonary bypass (CPB) were randomly divided into two equal groups: group C (control group, given with 4:1 blood containing cardioplegic liquid during the CPB) and group SF (Shenfu injection, receiving the blood containing cardioplegic liquid with 20 ml/L of Shenfu injection additionally). Blood samples were withdrawn from the central vein before operation, 30 minutes after aorta declamping, and 4, 12, and 24 hours after CPB, to test the serum cardiac troponin I (cTnI), creatine phosphokinase (CK), and creatine phosphokinase isoenzyme (CK-MB). The CK, CK-MB, and cTnI level were normal before operation and there were no significant differences in these indexes between the two groups. 30 minutes after aorta declamping, the CK, CK-MB, and cTnI levels were higher than those before operation in both groups (P < 0.05, P < 0. 01), and the higher levels remained to 24 hours after CPB. 24 hours after CPB, the CK level of the group SF was significantly lower than that of the group C (P < 0.05), and 30 minutes after aorta declamping to 24 h after CPB, the CK-MB and cTnI levels were lower in the group SF compared with the group C (all P < 0. 05). Shenfu injection decreases the level of CK, CK-MB and cTnI, and reduces the myocardial injury.

Protective effect of SHEN-FU injection on heart injury induced by ischemia/reperfusion

Aim: To clarify the effects of SHEN-FU injection on heart injury induced by ischemia/reperfusion in myocardial ischemia rats. Methods: Male Wistar rats were used to make the model of myocardial ischemia and reperfusion by ligation of the left descending coronary artery in the anaesthetized state. The rats were treated with SHEN-FU injection (i.v.1 mg/kg, 2 mg/kg) after the ischemia/reperfusion. Spectrophotometrical method was used to measure activities of Lactate dehydrogenase(LDH) and creatine kinase (CK) in serum, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and endothelial nitric oxide synthease (eNOS) as well as malondialdehyde (MDA) and NO levels in heart.