阿托伐他汀抗缺氧无血清条件下小鼠心肌干细胞凋亡的作用

Atorvastatin Decreases Apoptosis of Cardiac Stem Cells under Hypoxia and Serum Deprivation Conditions

目的在体外缺氧无血清条件下模拟心肌缺氧微环境,研究阿托伐他汀(Atorvastatin,ATV)对小鼠心肌干细胞(cardiac stem cells,CSCs)的抗凋亡作用及可能发挥作用的分子机制。方法分离培养小鼠CSCs,在缺氧无血清条件下用ATV处理12 h,应用流式细胞术和Hoechst 33342荧光染色观察细胞凋亡,并利用Western blotting方法检测通路蛋白单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的磷酸化水平。结果缺氧无血清条件引起明显的细胞凋亡,ATV处理组细胞凋亡率显著降低(p<0.05),且呈一定的浓度依赖性。ATV处理组AMPK磷酸化水平明显升高(p<0.05),加入AMPK阻断剂CompoundC可以显著阻断这种效应。结论在缺氧无血清条件下,一定浓度的ATV对CSCs具有显著抗凋亡作用,且AMPK/mTOR通路可能参与了该过程。

Objective To investigate the effect of Atorvastatin （ATV） on apoptosis of cardiac stem cells, and determine the underlying pathway under hypoxia and serum deprivation （HASD）. Methods Mouse CSCs were separated and cultured with the treatment of ATV for 12 h under hypoxia and serum deprivation. Apoptosis was detected by flow cytometry and Hoechst 33342 staining： Western blotting was used to detect the expressions of the phosphorylation of AMPK and mTOR. Results ATV decreased the apoptosis of CSCs concentration-dependently. Furthermore, ATV significantly enhanced the phosphorylation of AMPK（p〈0.05）, while the anti-apoptotic effect was attenuated by the AMPK inhibitor Compound C. Conclusion ATV inhibited H/SD-induced apoptosis in CSCs in concentration dependent manner, possibly linked to the activation of AMPK/mTOR pathway.