不同剂量辛伐他汀对多柔比星导致的乳鼠心肌细胞损伤的保护作用

目的探讨辛伐他汀（SIM）对多柔比星（DOX）损伤乳鼠心肌细胞的保护作用。方法新生SD大鼠（乳鼠）心肌细胞随机分为5组,对照组不予任何药物,正常培养;DOX组予1μmol/L DOX,SIM低、中、高剂量组分别在给予1μmol/L DOX基础上予11、0、20μmol/L SIM,继续培养24 h后,倒置相差显微镜下测定各组心肌细胞搏动频率,流式细胞术检测凋亡率,Western blot法检测钙释放通道（RyR2）蛋白表达情况。结果 DOX组及SIM低、中、高剂量组的心肌细胞搏动频率、RyR2表达均明显低于对照组,凋亡率均明显高于对照组,P均〈0.05;SIM低、中、高剂量组的心肌细胞搏动频率、RyR2表达均明显高于DOX组,凋亡率均明显低于DOX组,且呈剂量依赖性,P均〈0.05。结论 SIM对DOX损伤乳鼠心肌细胞有保护作用,且呈剂量依赖性,其机制可能与提高RyR2表达有关。

Protective effect of different doses of simvastatin on neonate rat cardiomyocyte injury induced by doxorubicin

Objective To investigate the protective effect of simvastatin（SIM） on neonate rat myocardium cell injury induced by doxorubicin（DOX）.Methods The cardiomyocytes of renewal SD rats（neonate rat） were divided randomly into five groups,control group was only given cell culture medium;DOX group was given DOX with the final concentration of 1 μmol/L;SIM groups of low,moderate and high dosage were given SIM with the final concentration of 1,10,20 μmol/L at the base of DOX group.After 24 hours further cultivation,the cardiomyocytes beating rate was determined by inverted phase contrast microscope,the apoptosis ratio of cardiomyocytes was detected by flow cytometry,expression of RyR2 protein was evaluated using Western blot.Results Compared to the control group,the cardiomyocytes beating rate and the synthesis of RyR2 were descended significantly in the DOX and SIM（low,moderate,high dosage）groups,and the apoptosis ratio of cardiomyocytes was increased significantly（all P〈0.05）.Compared to the DOX group,the cardiomyocytes beating rate and the expression of RyR2 protein were increased significantly in SIM（low,moderate,high）groups,and the apoptosis ratio of cardiomyocytes was descended significantly in a dose-dependent manner（all P〈0.05）.Conclusion SIM can protect neonate rat myocardium cell injury induced by DOX in a dose-dependent manner,the mechanism may be related to the up-regulation of RyR2 protein.