Shen-fu injection alleviates acute renal injury by reducing cytokine levels and modulating apoptosis in a porcine hemorrhagic shock model

ABSTRACT Purpose Shen-fu injection (SFI) was used to intervene in the resuscitation of porcine hemorrhagic shock (HS) model to study its protective effects on acute kidney injury. Methods After 60 min of HS, 28 animals were randomly assigned into four groups. The groups were as follows: hemorrhagic shock group (HS); HS resuscitation with shed-blood group (HSR); HS resuscitation with shed-blood and SFI (1 mL·kg-1) group (HSR-SFI); and the sham operation group (Sham). The bloods were analyzed for serum creatinine (sCr), cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL). BAX, Bcl-2, and caspase-3 protein expressions by Western blot analysis and immunohistochemical staining. The renal tissues were removed and pathologic changes were observed. Results Mean aortic pressure (MAP) in HSR-SFI groups were higher than that in HSR groups after shock. At the 6th hour after shock, the urine volume per hour in the HSR-SFI groups was more than that in the HSR groups. The sCr, NGAL, CysC and cytokine levels of HSR-SFI groups were lower. The Bcl-2 expression was increased in the HSR-SFI groups. The BAX and caspase-3 expressions were reduced. The histopathologic score in the HSR-SFI was lower. Conclusions SFI may reduce the risk of acute kidney injury (AKI) following hemorrhagic shock by attenuating systemic inflammatory responses, and regulating the expression of apoptosis-related proteins.

Effect of shenfu injection on isolated empty beating hearts from miniature pigs

Abstract Objective: To investigate the effect of Shenfu (SF) injection on donor heart preservation. Methods: Twelve pigs were randomly divided into SF group (n=6) and control group (n=6). After eight hours of perfusion, the differences in hemoglobin, the expression of Bcl-2 and BAX, and changes in the myocardial ultrastructure were compared to illustrate the effects of SF injection in heart preservation. Results: The differences in free hemoglobin between the SF group and the control group were statistically significant (P=0.001), and there was significant interaction of groups with times (P=0.019), but the perfusion time may not be associated with the hemoglobin concentration (P=0.616). According to Western blotting analysis, the expression of Bcl-2 was higher in the SF group than in the control group, while the expression of BAX was not different between the two groups. As to ultrastructural changes, both groups exhibited mitochondrial swelling and myofilament lysis, but the degree of damage in the SF group was smaller. Conclusion: Our study suggests that the application of SF injection for heart preservation may protect against cardiomyocytes and erythrocytes apoptosis, and Bcl-2 protein may play a role in these physiological processes.

Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients / 中国结合医学杂志

OBJECTIVE@#To investigate the hemodynamic effect of Shen-Fu Injection (, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO).@*METHODS@#All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation.@*RESULTS@#The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P0.05).@*CONCLUSION@#SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.

Microtox-based Fast Testing Method of Comprehensive Toxicity of Shen-Fu Injection / 世界科学技术-中医药现代化

In this research,Microtox technology was used to evaluate the comprehensive toxicity of Shen-Fu injection,which was an exclusive product of the pharmaceutical company.Firstly,vibrio fischeri was used as test strain.The best test system and methodology were identified.Under the best test conditions,vibrio fischeri was firstly used in the luminescent bacteria comprehensive toxicity of the exclusive product Shen-Fu injection.The results showed that in the 2 mL reaction system,the best recovery liquid volume was 0.9 mL/ freeze-dried vial,50 μL bacterial suspensions/ sample,the detection time was 10 min after adding bacterial suspensions,the pH was 5-10,the luminous intensity was 800 000-12 000 000 for 10 rin.The RSD of replication experiment and intermediate precision test was ? and ?,respectively,which fitted to the requirements.There was no significant difference on EC50 values among 9 batches of tested Shen-Fu injection (41.07％,RSD ＜ 5％).It was concluded that there was significant concentration-effect relationship between Shen-Fu injection and the toxicity of vibrio fischeri.There was no significant difference on EC50 values among different batches.It indicated that there was small quality volatility among different batches of Shen-Fu injection.The control on product manufacturing was strong.

Dose-Effect Relationship of Shen Fu Injection (SFI) Between Blood Viscosity and the Early-and Mid-Stage Cardiogenic Shock in Rats / 世界科学技术-中医药现代化

This study aimed at investigating the dose-effect relationship of SFI between the blood viscosity and the early-and mid-stage cardiogenic shock and the mediatory effect on rats.The end or root of left anterior descending coronary arteries (LADCA) was ligatured to establish the rat model of the early-and mid-stage cardiogenic shock.The blood viscosity indexes included low shear rate (LSR,10/s),middle shear rate (MSR,60/s),high shear rate (HSR,150/s) of the whole blood viscosity and plasma viscosity (PV),being observed 60 mins after the venous administration of 0.10,0.33,1.00,3.30,10.00 and 20.00 mL·kg-1 SFI (low dosage range:0.1-1.0 mL·kg-1,middle dosage range:1.0-10 mL·kg-1,high dosage range:10-20 mL·kg-1) with a blood rheometer.Dose-response curves were fitted by GraphPad Prism 6.0 software,the dose-response relationship of SFI between the blood viscosity and the early-and mid-stage cardiogenic shock in rats was evaluated to calculate the dose threshold parameters of the indexes.It was found that the blood viscosity indexes were improved with the dosage of 10 mL·kg-1 SFI in rats with the early-stage cardiogenic shock,while the dose-response curves of LSR,MSR and HSR at the early stage all presented favorable s shapes.Most of the effective dose range [D]2o-[D]80 and the threshold dose [D]20 were between 3.3 and 6.3 mL· kg-1.The four indexes of blood viscosity were improved with the administration of 10 and 20 mL·kg-1 SFI in mid-stage model rats with favorable s shapes in the dose-response curves.Most of the effective dose range and the threshold dose were in the range of 3.3 to 10.0 mL·kg-1.In conclusion,most of the dose-response curves of blood viscosity indexes in early-and mid-stage cardiogenic shock rats presented favorable s shapes with the threshold dose between 3.3 and 10.0 mL·kg-1,indicating an effective middle dosage range,which was converted into clinical dosage about 37.1 to 112 mL each day.The research provided an experimental basis for clinical medication.

Protective Effect of Shen Fu Injection on Cardiac Function in Sepsis Rats Through p38MAPK Pathway / 广州中医药大学学报

Objective To investigate the protective effect of Shen Fu Injection (SFI) on cardiac function in sepsis rats and to explore the possible mechanism.Methods Forty SD male rats were randomly divided into 4 groups,namely normal control group,sham operation group,model group,SFI group.The sepsis model was established by cecal ligation and puncture (CLP).Thirty-six hours later,the arterial blood and left ventricular myocardium tissues were collected,and then the serum levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1 were detected and the levels ofphosphorylated p38-mitogen-activated protein kinase (p-p38MAPK) and p38-mitogenactivated protein kinase (p38MAPK) in the supernatant of myocardial homogenate were detected.Results Thirty-six hours after modeling,left ventricular ejection fraction (LVEF) and left ventricular fractional shortening(LVFS) of the rats in the model group were significantly lower than those in the sham operation group (P ＜ 0.05).The heart function in SFI group was much improved compared with the model group (P ＜ 0.05).The serum TNF-α and IL-1 levels as well as p-p38/p38MAPK level in the supernatant of myocardial tissue of SFI group were lower than those in the model group (P ＜ 0.05).There were no significant differences of the above indexes between the sham operation group and the normal control group (P ＞ 0.05).Conclusion SFI has protective effect against sepsis myocardial injury.The mechanism may be related with the inhibition of p38MAPK phosphorylation in the myocardium,thereby reducing the release ofinflammatory cytokines in the pathway.

Fu-Fang Ku-Shen Injection in Combination with Modern Medications in Treating Lymphoma: A Real-world Study Based on Association Rules And Apriori Algorithm / 世界科学技术-中医药现代化

This study was aimed to investigate the application rrles of Fu-Fang Ku-Shen (FFKS) injection in combination with modern medicines for the treatment of lymphoma in the real world,in order to provide references for rational clinical application of effective medication.Patients diagnosed as lymphoma and treated with FFKS injection from 22 triple-A hospitals in China were enrolled as research objects.Patients' treatment data were extracted from the hospital information system,which was established by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,in order to analyze the frequency distribution characteristics of modern medications combined in the treatment.Association rules and Apriori algorithm were used in the analysis of association characteristics of medication combination.The results showed that 3 674 cases fit the inclusion criteria were searched from the data warehouse.In the clinical practice,FFKS injection was frequently combined with moderu medications,such as antibiotics,glucocorticoids,5-HT receptor antagonists,immunomodulatory drags,proton pump inhibitor,chemotherapeutic drugs,and hepatic protector.Its associated modern medication combination showed special rrles,which was in consistency with the related diagnosis and treatment of lymphoma guideline.It was concluded that FFKS injection combined with modern medicine in the treatment of lymphoma in the real world was basically in consistency with related guidelines.It was focused on reducing the side effects of chemotherapy,prolonging survival time,and improving quality of life.It provided references for rational clinical drag application of lymphoma.

Effects of Shen-Fu Injection () on apoptosis of regulatory T lymphocytes in spleen during post-resuscitation immune dysfunction in a porcine model of cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen.</p><p><b>METHODS</b>After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine (EP) group, and saline (SA) group (8 in each group), which received central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated (sham) group (n=6). After successful return of spontaneous circulation (ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05).</p><p><b>CONCLUSIONS</b>SFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.</p>

Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation.</p><p><b>METHODS</b>Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC.</p><p><b>RESULTS</b>Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups.</p><p><b>CONCLUSIONS</b>SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.</p>

Shen-Fu Injection () alleviates post-resuscitation myocardial dysfunction by up-regulating expression of sarcoplasmic reticulum Ca(2+)-ATPase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction.</p><p><b>METHODS</b>Ventricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined.</p><p><b>RESULTS</b>Cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>The administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.</p>

Protective effect and mechanism ofShenfu injection on the oxidaitve damage in PC12 cells induced by H2O2 / 国际中医中药杂志

Objective To investigate the effects and probable mechanism ofShenfu injection on the oxidaitve damage of H2O2-induced PC12 cells.Methods PC12 cells were cultured and exposed to 100μmol/L H2O2 for 1 h to establish the oxidative damage model. The protective effect ofShenfu injection was observed by the cell survival rate measured by colorimetric MTT assay, and the leakage rate of lactic dehydrogense (LDH). Western blot methods were used to detect the expression of NF-κB signaling pathway.Results Compared with the model group,Shenfu injection at 5, 10, 20 ml/L could improve the PC12 cells survival rate (83.11% ± 2.59 %, 87.99% ± 0.59%, 85.26% ± 1.07%vs. 73.82% ± 1.82%;P<0.01 orP<0.05), decrease the LDH leakage rate (32.75% ± 4.10%, 28.52% ± 1.14%, 35.79% ± 1.62%vs. 64.34% ± 3.18%;P<0.01 or P<0.05). Western blot results showed thatShenfu injection could protect the PC12 cells from oxidaitve damage by suppressing the p-p65/p65 (1.30 ± 0.10, 1.17 ± 0.06, 1.37 ± 0.15 vs. 1.70 ± 0.10;P<0.01 orP<0.05), p-IκBα/IκBα (1.07 ± 0.12, 1.00 ± 0.10, 1.03 ± 0.06 vs. 1.17 ± 0.06; P<0.01 orP<0.05).ConclusionShenfu injection has a obvious antioxidant effect on PC12 cells in vitro.

Effect of Shen-Fu Injection Pretreatment to Myocardial Metabolism During Untreated Ventricular Fibrillation in a Porcine Model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventricular fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardium.</p><p><b>METHODS</b>Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection; the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na + -K + -ATPase and Ca2 + -ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals.</p><p><b>RESULTS</b>The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levels of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATP, ADP, and phosphocreatine in the SFI group was higher than those in the SA group. The activity of LV Na + -K + -ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significantly lower in the SA and SFI groups at 8- and 12-min compared with 4-min. The AMSA in the SFI group was higher than that in the SA group at each time point during untreated VF.</p><p><b>CONCLUSIONS</b>SFI pretreatment can improve myocardial metabolism and reduce energy exhaustion during VF, and it does not aggravate the excessive secretion of endogenous CAs.</p>

Comparison of epinephrine and Shen-Fu injection on resuscitation outcomes in a porcine model of prolonged cardiac arrest / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epinephrine has been used as a first-choice vasopressor drug for cardiac arrest (CA) since 1974. However, the administration of epinephrine is controversial. This study aims to compare the effects of Shen-Fu injection (SFI) and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.</p><p><b>METHODS</b>Ventricular fibrillation (VF) was electrically induced. After 8 minutes of untreated VF and 2 minutes of chest compressions, 24 pigs were randomly divided into 3 groups (n = 8 per group): central venous injection of SFI (SFI group), epinephrine (EPI group), or saline solution (SA group). The haemodynamic status and oxygen metabolism parameters, including cardiac output, mean arterial pressure, left ventricular dp/dtmax and negative dp/dtmax, oxygen delivery (DO2), and oxygen consumption (VO2), were calculated.</p><p><b>RESULTS</b>SFI shortened the time to restoration of spontaneous circulation (ROSC) and decreased the number of shocks, similar to epinephrine. However, the mean arterial pressure, cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC. VO2 and ERO2 decreased after ROSC and then increased. VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC, while those were lowest in the EPI group among all groups.</p><p><b>CONCLUSIONS</b>SFI shortened the time to ROSC and decreased the number of shocks, similar to epinephrine. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with epinephrine. SFI might be a potentially vasopressor drug for the treatment of CA.</p>

Effect of Shenfu injection on the expressions of ORP150, XBP1 and CHOP mRNAs in hypoxic-ischemic neonatal rats / 国际脑血管病杂志

Objective To investigate the effect of Shenfu injection on the expressions of endoplasmic reticulum stress-related factors oxygen-regulated protein 150 (ORP150),X-box binding protein 1 (XBP1),and C/EBP homologous protein (CHOP) mRNAs in cerebral cortical neurons after hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods The 7 day-newborn Sprague-Dawley rats were randomly divided into sham operation,normal saline and Shenfu treatment (Shenfu injection,10 ml/kg per day,peritoneal injection,for 3 days) groups.They were redivided into 3 h,6 h,12 h,24 h,3 d and 7 d subgroups at different time points after modeling (n =8 in each group).A HIBD model of the neonatal rats was induced.Reverse transcription-polymerase chain reaction was used to detect the expressions of ORP150,XBP1,and CHOP mRNAs in rat cerebral cortex.Results The expressions of ORP150,XBP1 and CHOP mRNAs of the sham operation group was very week.The expressions of ORP150,XBP1 and CHOP mRNAs in the normal saline group and the Shenfu treatment group were significantly upregulated compared to those in the sham operation group at 3 h after modeling (all P ＜0.05); the expressions of XBP1 and CHOP mRNAs reached the peak at 6 and 12 h,respectively.Then they decreased mildly and closed to the level in the sham operation group at day 7.The expressions of XBP1 and CHOP mRNAs in the Shenfu treatment group at 12,24 h and day 3 after modeling were significantly lower than those in the normal saline group (all P ＜0.05).The XBP1 mRNA expression was significantly positively correlated with the CHOP mRNA expression in the normal saline group (r =0.649,P ＜0.05).Conclusions HIBD in neonatal rats induces endoplasmic reticulum stress response.ORP150,XBP1 and CHOP may be involved in the delayed neuronal damage process after HIBD in neonatal rats.Shenfu injection downregulates the expression of XBP1 and CHOP mRNAs and inhibits endoplasmic reticulum stress response.

Shen-Fu injection reduces impaired myocardial β-adrenergic receptor signaling after cardiopulmonary resuscitation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Post-resuscitation myocardial dysfunction has been implicated as a major cause of fatal outcome in patients who survive initially successful cardiopulmonary resuscitation (CPR). In our previous study, we found that impaired myocardial β-adrenergic receptor (AR) signaling is a key mechanism in post-resuscitation myocardial dysfunction and Shen-Fu injection (SFI) can attenuate post-resuscitation myocardial dysfunction. However, whether SFI can prevent impaired post-resuscitation myocardial β-AR signaling is not yet known. In this study, we investigated the effect of SFI on impaired myocardial β-AR signaling occurring post-resuscitation in a porcine model of cardiac arrest.</p><p><b>METHODS</b>Ventricular fibrillation was induced electrically in anesthetized male landrace domestic pigs. After 4 minutes of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI (0.5 ml/min; n = 8) or saline (placebo; n = 8) for 6 hours, beginning 15 minutes after the return of spontaneous circulation (ROSC). Hemodynamic and echocardiographic data were recorded. β-AR signaling was assessed at 6 hours after the intervention by measuring myocardial adenylate cyclase activity, β-AR density and β-AR kinase expression.</p><p><b>RESULTS</b>Treatment with SFI produced better maximum rate of left ventricular pressure increase (dp/dt(max)) and maximum rate of left ventricular pressure decline (-dp/dt(max)), cardiac output, and ejection fraction after ROSC. SFI treatment was also associated with lower myocardial β-adrenergic receptor kinase expression, whereas basal and isoproterenol-stimulated adenylate cyclase activity and the total β-AR density were significantly increased in the SFI group when compared with the placebo group.</p><p><b>CONCLUSION</b>SFI attenuated post-resuscitation myocardial dysfunction by preventing impaired myocardial β-AR signaling after CPR.</p>

Expert Survey on Application of Traditional Chinese Medicine in Different Clinical Classifications of Coronary Heart Disease / 世界科学技术-中医药现代化

This study was aimed to take an expert survey on the application of traditional Chinese medicine (TCM) in different clinical classifications of coronary heart disease (CHD) in order to master its medication characteristics and principles . Delphi method was applied in different clinical classifications of CHD , which contain angina pectoris, acute myocardial infarction, heart failure, arrhythmia, after percutaneous coronary inter-vention ( PCI ) and after coronary artery bypass graft ( CABG ) . Two rounds of nationwide expert survey were giv-en on the commonly-used TCM decoction , oral administration of TCM patent drugs and TCM intravenous preparations in CHD treatment . The results showed that TCM medications in the treatment of angina pectoris contain Xuefu Zhuyu decoction, Gualou Xiebai Banxia decoction, Tongxinluo capsules, Compound Danshen dripping pills, Shexiang Baoxin pill, Danshen injection, Danhong injection, and etc. And commonly used TCM medications for the treatment of acute myocardial infarction include Xue fu Zhuyu decoction , Gualou Xiebai Banxia decoction, Compound Danshen dripping pills, Shexiang Baoxin pill, Suxiao Jiuxin pills, Shengmai injec-tion , She nmai injection and so on . Heart failure of CHD was treated by Zhenwu decoction , Qili Qiangxin cap-sule, Qishen Yiqi dripping pills, Shenfu injection, Shengmai injection, Shenmai injection and so on. TCM treatments of arrhythmia of CHD usually include Zhigancao decoction , Tianwang Buxin boluses , Wenxin gran-ules, Shensong Yangxin capsule, Shengmai injection, Shenmai injection and so on. The commonly used TCM medications after PCI contain Xuefu Zhuyu decoction, Tongxinluo capsules, Compound Danshen dripping pills, Shengmai injection and Danshen injection and so on. Commonly used TCM medications after CABG include Xuefu Zhuyu decoction, Buyang Huanwu decoction, Tongxinluo capsules, Shexiang Baoxin pill, Compound Dan-shen dripping pills, Shengmai injection and Danhong injection and so on. It was concluded that different clini-cal classifications of CHD had characteristics and commonness in the application of TCM . Findings based on expert consensus through the survey provide certain reference values in the clinical syndrome differentiation of CHD .

Protective effect of Shen fu injection against intestinal barrier dysfunction and second hit in rats with severe acute pancreatitis / 第二军医大学学报

Objective: To evaluate the protective effect of Shenfu injection (SFI) against intestinal barrier dysfunction and second hit in rats with severe acute pancreatitis (SAP). Methods: Fifty-four male Wistar rats were randomly divided into sham operation group (n = 6), SAP group (n = 24), and SAP + SFI group (10 ml/kg body wt, n = 24). Sham operation group underwent laparotomy only. SAP model was established by retrograde injection of 5% sodium taurocholate into the bilipancreatic duct of Wistar rats. SAP+SFI group was given SFI (10 ml/kg) intaperitoneally 2 h before SAP establishment. Rats were sacrificed at 3,6,12 and 24 hours after operation. The samples of pancreas, lung and liver were collected for measuring the levels of myeloperoxidase (MPO) at 3,6,12, and 24 h after injection of sodium taurocholate. The pathological changes of the terminal ilea were observed under light microscopy, and the blood levels of diamine oxidase (DAO), tumor necrosis factor alpha (TNF-α) and interleukin-6(IL-6) were also measured at different time points. Results: The blood levels of TNF-α, IL-6 and DAO in SAP group were significantly higher than those in the sham operation group at all time points (P<0.01). The levels of intrapulmonary, intrapancreatic and intrahepatic MPO in SAP group were significantly than those in the sham operation group at 6,12, and 24 hours (P<0.01). The contents of DAO, TNF-α and IL-6 were significantly decreased in SAP + SFI group compared with in SAP group at all time points (P<0.05 or P<0.01). The contents of intrapulmonary, intrapancreatic and intrahepatic MPO were significantly decreased in SAP+SFI group compared with SAP group at 6,12, and 24 h after operation (P<0.05 or P<0.01). Intestinal pathological damages were obviously milder in SAP+SFI group than that in SAP group at 24 h after operation. Conclusion: SFI can protect the small intestine mucosal barrier and other organs from second hit by reducing the polymorphonuclear leucocyte detaining and inhibiting TNF-α and IL-6.

Effects of Shen-fu injection pretreatment on mitochondrial permeability transition and transmembrane potential following myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effects of pretreatment with Shen-fu injection on mitochondrial permeability transition and mitochondrial transmembrane potential (△ψm) following myocardial ischemiareperfusion (IR) injury in rats. Methods Thirty SD rats of both sexes weighing 250-300 g were randomly divided into3 groups with 10 animals in each group:Ⅰ sham operation group (group S); Ⅱ IR group and Ⅲ Shen-fu injection group (group SFI). The animals were anesthetized with intraperitoneal 20% urethane 5 ml/kg. The chest was opened and the heart exposed. Myocardial IR was induced by temporary ligation of the anterior descending branch of left coronary artery maintained for 30 min, followed by 120 min reperfusion. Myocardial ischemia was confirmed by decoloration of apex and elevation of S-T segment (＞ 0.1 mV) or erection of T wave. In group SFI,SFI 10 ml/kg was infused at 15 min before ischemia, while in group S and IR equal volume of normal saline was infused instead of SFI. At 120 min of reperfusion, blood samples were collected from right internal carotid artery for determination of serum concentration of cTnI. The animals were then sacrificed and the hearts were immediately removed for measurement of myocardial mitochonerial permeability transition pore (MPTP) activity (by spectrophotometry at 540 nm) and myocardial △ψm (by fluorospectrophotometer using rhodamine 123 as fluorescent probe). Results Compared with group S, serum cTnI concentration and MPTP activity were significantly increased and △ψm was decreased in group IR. SFI pretreatment significantly attenuated the IRinduced increase in serum cTnI concentration and the MPTP activity and decrease in △ψm. Conclusion SFI pretreatment can protect myocardium from IR injury by attenuating the IR induced increase in MPTP opening and decrease in △ψm.

Effect of Shen-fu injection on pulmonary contusion rabbits / 中国基层医药

Objective To investigate the effects of Shen-fu injection on pulmonary contusion rabbits. Meth-ods Sixteen rabbits were randomly divided into 2 groups: the treatment group (Shen-fu group) and the control group. The animals were induced the pulmonary contusion models. After 60min, the animals in Shen-fu group re-ceived Shen-fu injection received 5 ml/kg, and those in control group 5 ml/kg LRS. The animals were killed six hours later, the right lung tissue wet-to-dry (W/D) ratio and myeloperoxidase (MPO) activity were obtained,the pro-tein expression of nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) were also detec-ted. Results The lung tissue W/D, MPO, and the protein expression of NF-κB and ICAM-1 were decreased evi-dently in Shen-fu group (P<0. 01). The morphologic and ultrastructural damages in Shen-fu group were milder than in control group. Conclusion Shen-fu injection is effective on pulmonary contusion rabbits.

Effects of Shen-fu on the activity of β-adrenoreceptors in cardiopulmonary resuscitation rats / 中华急诊医学杂志

Objective To study the effects of Shen-fuinjection onthe activity of β-adrenoreceptor in SD rats with cardiopulmonary resuscitation. Method The exprimerit was done at emergency medical lab of Shanghai Changzheng hospital.Cardiac arrest was induced thngh asphyxiation(succinylcholine)and ice-cold 0.5 mol/L KCI in rats,and resuscitation began at five minutes after cardiac orrest.In this experiment,seventy-two male SD rats were randomizly divided into 9 groups:control group(sham group),routine treatment(O.5 h,2 h,4 h,6 h) groups.and Shen-fu treatment(O.5 h,2 h,4 h,6 h),and each group had 8 rats.Rats of Shen-fh treatment groups were injected with shen-fu(20 mL/kg,20 mL/h)during CPR.3H-prazosln Wag used to determine the activity of β-adrenoreceptor in myocyte. The data of the statistic analysiswere presentedin the for mofmeaj14-standard(4-5)deviation.One-way ANOVA was used for muhig Toup comparison,and t-test for comprarison between two groups.Results[3-adrenoreeeptor reached peak at0.5 h after CPR(247.81±8.91)fmol/mg,reached the lowest level at 4 h(104.17 4-13.87)fmol/mg,and returned to the normal level at 6 h(178.53±10.42)fmol/mg.In the eady period.-adrenorecepter activity in control group[O.5 h:(259.91-4-18.09)finol/mJ was similar to that in Shenfu treatment groups(P>O.05).In the late phase,adrenoreeeptor activity in the Shen-fu treatment groups[2 h:(173.04±18.77)fmol/mg,4 h:(148.72±13.88)finoL/mg]was significantly hi#er than that in the control groups(P<0.05).Conclusiom After CPR, ceplor activity firstly rises and then declines,and Shenfu injection Call significantly increase adrenoreceptor activity of mrs in the later period after CPR.