Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti-vation after coronary microembolization(CME)in rats.Methods Fifty rats were randomly divided into five groups;th...Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti-vation after coronary microembolization(CME)in rats.Methods Fifty rats were randomly divided into five groups;the coronary microembolization(CME)group,the sham-operated(sham)control group,the gastric lavage control group,the atorvastatin lavage group,and the caspasse-8 inhibitor(N-acetyl-Ile-Glu-Thr-Asp-CHO,abbreviated as CHO)group,with 10 rats for each group.A microembolization ball was injected through the left ventricle for constructing the CME model.Animals in the sham control group were given an injection of physiological saline instead of the microembolization ball.Seven days before the operation,the atorvastatin group underwent gastric lavage with 20 mg/kg of atorvastatin once a day.Gastric lavage control animals underwent gastric lavage with an equivalent dose of physiological saline instead of the atorvastatin.Animals in the CHO group were given an intraperitoneal injection of 10 mg/kg of CHO 30 min before the operation.Six hours after the operation,cardiac ultrasonic detection was conducted on each group to measure the cardiac function indexes.TUNEL(Terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling)assays were used to measure myocardial apoptosis,and western blots were used to quantify the expression levels of activated caspase-3 and-8.Results(1)The echocardiographic parameters showed that,compared to the sham control animals,the left ventricular ejection fraction(LVEF)of the CME group was significantly decreased(P【0.05).In addition,cardiac sonography revealed a decrease in the left ventricular shortening fraction(FS)and cardiac output(CO),but an increase in the left ventricular end-diastolic dimension(LVEDd).Compared to the CME group,the atorvastatin and CHO groups exhibited significantly improved cardiac function(P【0.05).(2)When compared with the sham control,the myocardical apoptotic rate of the CME group,as well as the levels of activated caspase-3 and-8,increased significantly(P【0.05).The myocardial apoptotic rate,as well as the levels of activated caspase-3 and caspase-8 in the atorvastatin and CHO groups,decreased significantly(P【0.05)in comparison to the CME group.Conclusions The atorvastatin pretreatment clearly suppressed post-CME myocardial apoptosis and improved cardiac function.The most likely mechanism for these effects is the blockade of the myocardial death receptor-mediated apoptosis pathway.展开更多
文摘Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti-vation after coronary microembolization(CME)in rats.Methods Fifty rats were randomly divided into five groups;the coronary microembolization(CME)group,the sham-operated(sham)control group,the gastric lavage control group,the atorvastatin lavage group,and the caspasse-8 inhibitor(N-acetyl-Ile-Glu-Thr-Asp-CHO,abbreviated as CHO)group,with 10 rats for each group.A microembolization ball was injected through the left ventricle for constructing the CME model.Animals in the sham control group were given an injection of physiological saline instead of the microembolization ball.Seven days before the operation,the atorvastatin group underwent gastric lavage with 20 mg/kg of atorvastatin once a day.Gastric lavage control animals underwent gastric lavage with an equivalent dose of physiological saline instead of the atorvastatin.Animals in the CHO group were given an intraperitoneal injection of 10 mg/kg of CHO 30 min before the operation.Six hours after the operation,cardiac ultrasonic detection was conducted on each group to measure the cardiac function indexes.TUNEL(Terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling)assays were used to measure myocardial apoptosis,and western blots were used to quantify the expression levels of activated caspase-3 and-8.Results(1)The echocardiographic parameters showed that,compared to the sham control animals,the left ventricular ejection fraction(LVEF)of the CME group was significantly decreased(P【0.05).In addition,cardiac sonography revealed a decrease in the left ventricular shortening fraction(FS)and cardiac output(CO),but an increase in the left ventricular end-diastolic dimension(LVEDd).Compared to the CME group,the atorvastatin and CHO groups exhibited significantly improved cardiac function(P【0.05).(2)When compared with the sham control,the myocardical apoptotic rate of the CME group,as well as the levels of activated caspase-3 and-8,increased significantly(P【0.05).The myocardial apoptotic rate,as well as the levels of activated caspase-3 and caspase-8 in the atorvastatin and CHO groups,decreased significantly(P【0.05)in comparison to the CME group.Conclusions The atorvastatin pretreatment clearly suppressed post-CME myocardial apoptosis and improved cardiac function.The most likely mechanism for these effects is the blockade of the myocardial death receptor-mediated apoptosis pathway.
