辛伐他汀对多柔比星损伤心肌细胞钙稳态作用的研究

Effect of simvastatin on the calcium homeostasis of myocardium cell injury induced by doxorubicin

目的:探讨辛伐他汀(simvastatin,SIM)对多柔比星(doxorubicin,DOX)损伤心肌细胞的保护作用。方法:将培养72 h的新生SD大鼠心肌细胞随机分为对照组、DOX损伤组、1μmol/L SIM干预组、10μmol/L SIM干预组、20μmol/L SIM干预组,继续培养24 h后,四甲基偶氮唑盐(MTT)检测心肌细胞存活率;荧光染料Fluo-3/AM检测心肌细胞内钙离子荧光强度;蛋白质印迹法检测肌浆网Ca2+-ATP酶(SERCA2a)的表达。结果:与对照组相比,DOX损伤组心肌细胞存活率明显下降(P<0.01);钙离子荧光强度明显增强(P<0.01);SERCA2a蛋白表达显著下降(P<0.01)。给予SIM处理后,心肌细胞存活率显著上升(P<0.01),钙离子荧光强度显著下降(P<0.01),SERCA2a表达明显改善(P<0.01)。结论:辛伐他汀对多柔比星损伤的心肌细胞的保护作用可能与部分改善SERCA2a的表达、抑制钙超载有关。

Objective： To investigate the protection effect of simvastatin（SIM）on the myocardium cell injury induced by doxorubicin（DOX）.Methods： The neonatal SD rats cardiomyocytes cultured for 72 hours were divided randomly into five groups： control group,DOX damnified group,DOX＋SIM（1 μmol/L）group,and DOX＋SIM（10 μmol/L）group,and DOX＋SIM（20 μmol/L）group.After 24 hours further cultivation,the survival ratio of cardiomyocytes were determined by MTT assay;detecting the [ Ca^2＋ ] i fluorescence intensity by Fluo-3/AM,and Western blot was used to evaluate SERCA2a protein synthesis.Results： Compared to the control group,in the DOX group,the survival ratio of cardiomyocytes were significantly descended（P〈0.01）;the [ Ca^2＋ ] i fluorescence intensity was significantly increased（P〈0.01）,the synthesis of SERCA2a was significantly descended（P〈0.01）.Compared to the DOX group,in the SIM groups,the survival ratio of cardiomyocyte was significantly increased（P〈0.01）,the [ Ca^2＋ ] i fluorescence intensity was significantly descended（P〈0.01）,the synthesis of SERCA2a protein was obviously ameliorated（P〈0.01）.Conclusion： SIM can protect myocardium cell injury induced by DOX,which may be related to partly by ameliorate the synthesis of SERCA2a and the inhibition of calcium overloading.