辛伐他汀对多柔比星损伤心肌细胞钙稳态作用的研究

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。

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

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 Ca2+ ] 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 Ca2+ ] 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 Ca2+ ] 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.