Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. ATPase 2a （SERCA2a） in a pig model with post-resuscitation myocardial dysfunction. Meth...Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. ATPase 2a （SERCA2a） in a pig model with post-resuscitation myocardial dysfunction. Methods： 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 t~ g/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 rain 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 13 1-adrenoceptor （AR） and SERCA 2a were determined. Results： Cardiac output, left ventricular dp/dtr,~x and negative dp/dtm^x were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of 13 1-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）. Conclusions： 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.展开更多
Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF ...Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.展开更多
文摘Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. ATPase 2a （SERCA2a） in a pig model with post-resuscitation myocardial dysfunction. Methods： 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 t~ g/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 rain 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 13 1-adrenoceptor （AR） and SERCA 2a were determined. Results： Cardiac output, left ventricular dp/dtr,~x and negative dp/dtm^x were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of 13 1-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）. Conclusions： 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.
基金Supported by the National Natural Science Foundation of China(No.81530100,81470191,and 81302908)
文摘Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.
