Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi-110062, India.
Int J Cardiol. 2011 Jul 15;150(2):193-200. doi: 10.1016/j.ijcard.2010.04.008. Epub 2010 May 7.
Apoptosis is a key pathologic feature in myocardial infarction and heart failure. Recent evidence suggests that statins may have beneficial effects on cardiovascular outcomes in patients with heart failure. The present study was planned to investigate the anti-apoptotic potential of rosuvastatin pretreatment in doxorubicin-induced cardiomyopathy.
Sixty male Wistar rats were randomly divided into six groups: Group-I (vehicle control group), Group-II (pathological Control group), Group-III (rosuvastatin 0.5 mg/kg), Group IV (rosuvastatin 2 mg/kg), Group-V (rosuvastatin 2 mg/kg per se), and Group-VI (carvedilol 1mg/kg). Myocardial apoptosis was detected by caspase-3 assay, DNA gel electrophoresis and Na(+)/K(+) ATPase estimation. The animals were evaluated for various biochemical parameters in serum followed by histopathological studies of heart tissue.
Doxorubicin treated rats exhibited cardiac dysfunctions as indicated by an increase in systolic, diastolic, mean BP, heart rate and tail blood flow and volume and increased serum LDH, TC, TGs, LDL-C, VLDL-C levels and atherogenic indexes. A marked induction in caspase-3 and Na(+)-K(+) ATPase levels and DNA laddering as revealed by agarose gel electrophoresis was observed in rat myocardium of pathological group. Pretreatment with the test drug, rosuvastatin significantly reduced the increase in hemodynamic parameters, serum LDH, lipid profile and myocardial caspase-3, Na(+)-K(+) ATPase activity as compared to the pathogenic control group. Further, DNA ladder formation was attenuated by rosuvastatin treatment. Histopathological studies further confirm its myocardial salvaging effects. The results were comparable with carvedilol.
The study demonstrates the cardioprotective potential of rosuvastatin against doxorubicin-induced myocardial apoptosis.
细胞凋亡是心肌梗死和心力衰竭的一个关键病理特征。最近的证据表明，他汀类药物可能对心力衰竭患者的心血管结局有有益的影响。本研究旨在探讨瑞舒伐他汀预处理对阿霉素诱导的心肌病的抗凋亡作用。
60 只雄性 Wistar 大鼠随机分为 6 组：第 I 组（载体对照组）、第 II 组（病理对照组）、第 III 组（瑞舒伐他汀 0.5mg/kg）、第 IV 组（瑞舒伐他汀 2mg/kg）、第 V 组（瑞舒伐他汀 2mg/kg 本身）和第 VI 组（卡维地洛 1mg/kg）。通过 caspase-3 测定、DNA 凝胶电泳和 Na(+)/K(+)ATP 酶测定检测心肌细胞凋亡。评估动物血清中的各种生化参数，然后对心脏组织进行组织病理学研究。
阿霉素处理的大鼠表现出心脏功能障碍，表现为收缩压、舒张压、平均血压、心率和尾血流和体积增加，血清 LDH、TC、TGs、LDL-C、VLDL-C 水平和致动脉粥样硬化指数升高。病理组大鼠心肌中 caspase-3 和 Na(+)-K(+)ATP 酶水平和 DNA 梯状带的诱导明显增加。与病理对照组相比，试验药物瑞舒伐他汀预处理显著降低了血流动力学参数、血清 LDH、血脂谱和心肌 caspase-3、Na(+)-K(+)ATP 酶活性的增加。此外，瑞舒伐他汀治疗可减弱 DNA 梯状带的形成。组织病理学研究进一步证实了其心肌保护作用。结果与卡维地洛相当。
本研究表明，瑞舒伐他汀对阿霉素诱导的心肌细胞凋亡具有心脏保护作用。
