缺氧诱导P21表达上调抑制大鼠胚胎H9C2心肌细胞增殖

Hypoxia-inducible P21 expression inhibiting proliferation of rat embryonic H9C2 myocardial cells

目的:探讨心肌梗死条件下抑制心肌细胞增殖的机制。方法:以缺氧环境培养的大鼠胚胎H9C2细胞为模型,研究心肌梗死和梗死后心肌细胞的增殖调控机制。结果:低氧培养诱导H9C2细胞内细胞周期调控蛋白P21表达上调,发生G1期细胞周期阻滞和细胞增殖抑制;恢复正常培养,则P21表达也回归正常水平,G1期细胞周期阻滞解除,细胞增殖恢复。采用si-RNA干扰P21表达,则解除了低氧诱导的G1期细胞周期阻滞,并显著缓解了低氧诱导的细胞增殖抑制。结论:P21是低氧诱导H9C2细胞增殖抑制的关键因子,抑制P21表达能促进急性心肌梗死后心肌功能恢复。

Objective：To study the mechanism of cardiomyocyte proliferation inhibition under acute myocardial infarction.Method：Rat embryonic H9c2 cells cultured under hypoxia were used to investigate the mechanism of cardiomyocytes proliferation under acute myocardial infarction or alleviation of acute myocardial infarction.Result：The cell cycle G1 arrested and proliferation inhibited with the up-regulation of P21 when H9c2cells exposed to hypoxia.However P21 expression returned to normal level,cell cycle G1-arrest was eliminated and cells recover to growth after H9c2 cells exposed to normoxia again.Furtermore,the cell cycle G1-arrest and growth inhibition in H9c2 cells were alleviated significantly when P21 gene was knock-down with siRNA.Conclusion：P21plays a vital role in hypoxia induced H9c2 cell growth inhibition,and inhibition P21 could be a new target to promote cardiac function recovery after acute myocardial infarction.