热休克蛋白27通过减少氧化应激和蛋白质泛素化水平延缓心脏衰老

Heat shock protein 27 alleviates cardiac aging by reducing oxidative stress and antagonizing protein ubiquitination

目的 探寻热休克蛋白27(HSP27)在改善由年龄引起的心脏老化过程中涉及的机制。方法 以HSP27心脏特异性表达的高龄转基因小鼠(Tg)以及对应的野生型小鼠(WT)作为研究对象(每组6只,雌雄性各3只),通过Masson染色了解心脏纤维化水平,蛋白质羰基化实验探寻氧化应激水平,Western-blot法检测心脏衰老指标p16、p21,探寻HSP27延缓心脏衰老涉及的机制。结果 高龄Tg心脏心肌间质纤维化面积比例较WT组减少[(0.072±0.019)%比(0.301±0.023)%,t=7.642,P=0.002],心脏活性氧自由基(ROS)含量较WT组降低[(100.3±1.3)比(203.9±6.1)U/μg,t=14.220,P<0.001],同时高龄Tg心肌蛋白质羰基化水平和蛋白质泛素化水平较WT组降低(均P<0.01)。结论 适当提高HSP27的表达可延缓心脏衰老,其机制可能涉及降低心肌氧化应激程度和蛋白质泛素化水平。

Objective To explore the mechanism of heat shock protein 27(HSP27) in alleviating cardiac aging. Methods Transgenic mice with heart-specific expression of HSP27(Tg) and corresponding wild-type mice(WT) were used as research objects(n=6, 3 males, 3 females). The level of cardiac fibrosis was obtained by Masson staining, the level of oxidative stress was explored by protein carbonylation experiments, and the cardiac aging indexes p16 and p21 were detected by Western-blot method to explore the mechanism of HSP27 delaying cardiac aging. Results The myocardial interstitial fibrosis of aged Tg mice was lower than that of WT mice [(0.072±0.019)% vs(0.301±0.023)%, t=7.642, P=0.002]. The reactive oxygen species(ROS) content in the heart of aged Tg mice was lower than WT mice [(100.3±1.3) vs(203.9±6.1)U/μg, t=14.220,P<0.001]. The protein carbonylation and ubiquitination level in the heart of aged Tg mice were significantly decreased than that of aged WT mice(both P<0.01). Conclusion Appropriately increasing the expression of HSP27 can delay cardiac aging, and its mechanism may involve decreasing the degree of myocardial oxidative stress and protein ubiquitination.