摘要
目的体外以缺氧无血清条件模拟心肌梗死后的心脏缺血微环境,研究洛伐他汀是否能够抑制缺氧无血清引起的骨髓间充质干细胞(MSCs)凋亡。方法以Hoechst33342染色法及Annexin V/PI流式细胞术检测洛伐他汀的抗凋亡作用,检测线粒体膜电位变化,进一步采用Western blot方法检测洛伐他汀对细胞色素C释放及caspase-3活化的影响。结果洛伐他汀0.01～1μmol/L能够有效地抑制缺氧无血清引起的MSCs凋亡。洛伐他汀抑制线粒体凋亡途径,增强线粒体膜电位水平、抑制细胞色素C释放,降低caspase-3活化水平。结论洛伐他汀能够抑制线粒体途径介导的凋亡,阻止caspase-3的活化,发挥抗缺氧无血清引起的MSCs凋亡,为提高移植干细胞的存活率提供了一种可能有效的干预措施。
Objective To investigate the effect of lovastatin on rat bone marrow mesenchymal stem cells （MSCs） apoptosis induced by hypoxia and serum deprivation （Hypoxia/SD） in vitro, focusing in particular on regulation of mitochondrial apoptotic pathway, and to find the useful therapeutic methods to increase transplanted MSCs survival. Methods MSCs were isolated from bone marrow of Sprague-Dawley rats. The anti apoptotic effects of lovastatin were detected using Hoechst33342 and Annexin V-FITC/PI binding assay by flow cytometric analysis. The cytochrome C and the activation of caspase-3 were detected by Western blot. Results Lovastatin（0. 01-1μmol/L）remarkably prevented MSCs from hypoxia/SD-induced apoptosis through inhibition of the mitochondrial apoptotic path- way, leading to attenuation of caspase-3 activation. The loss of mitochondrial membrane potential and cytochrome C release from mitochondria to cytosol were significantly inhibited by lovastatin. Conclusion Lovastatin protects MSCs from hypoxia/SD-induced apoptosis via inhibiting mitochondrial pathway, suggesting that it may provide a useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.
出处
《中华老年多器官疾病杂志》
2009年第3期259-264,268,共7页
Chinese Journal of Multiple Organ Diseases in the Elderly
