PPARα与人心肌细胞衰老及缺血再灌注损伤的相关性研究

Research of PPARα in human myocardial cell senescence and ischemia-reperfusion injury

目的寻找到一种与人类心肌细胞衰老及缺血再灌注损伤相关的基因或蛋白,为增强老年人心肌细胞抗缺血再灌注损伤能力、提高心外科治疗效果提供依据。方法经我院伦理委员会批准、术前签订知情同意书,对心脏外科术中需心脏停跳的年轻(5~10岁)及老年(60岁以上)患者,分别切取停跳前后废弃的心房肌组织约1 cm×1 cm,应用Real time PCR及Western blot技术检测和比较年轻与老年人心肌细胞中氧化物酶增殖激活的受体α(PPARα)的表达水平差异,并进一步分析缺血再灌注前后PPARα含量在不同年龄患者心肌中的变化情况。结果通过对比年轻及老年人的心肌细胞中PPARα在mRNA和蛋白表达水平上的差异,可见老年人心肌细胞中PPARα的mRNA和蛋白表达水平明显低于年轻人(P<0.05);年轻和老年人心肌组织中PPARα的mRNA表达水平在经历缺血再灌注损伤后均明显增加,并且年轻人心肌组织中PPARα的mRNA表达增加的比例明显高于老年人(P<0.05);年轻和老年人心肌组织中PPARα蛋白含量在经历缺血再灌注损伤后均明显增加,但本次研究中年轻人心肌组织中PPARα蛋白含量的增加比例与老年人相比并未发现明显差异。结论随着年龄的增加,人心肌细胞中PPARα基因含量及蛋白表达明显减少,而当年轻人及老年人心肌细胞在遭到缺血再灌注损伤时,PPARα基因含量及蛋白表达均明显增加,其中年轻人心脏中的PPARα在损伤时增加的较老年人可能更为明显。

Objective To find a gene or protein associated with aging and ischemia-reperfusion injury in human cardiomyocytes,thereby enhancing the ability of elderly cardiomyocytes to resist ischemia-reperfusion injury and improving the effect of cardiac surgery in such patients.Methods Approved by the ethics committee of our hospital and signed informed consent before surgery,1 cm×1 cm atrial muscle tissue of the young(5 to 10 years old)and elderly(over 60 years old)patients were cut off respectively before and after cardiac arrest.Realtime PCR and Western blot were used to detect and compare the expression levels of PPARαin young and elderly cardiomyocytes,and further analyzed the PPARαcontent before and after ischemia-reperfusion in patients with different ages.Results The mRNA and protein expression levels of PPARαcompared by realtime-PCR and Western blot in elderly cardiomyocytes were significantly lower than those in young adults.The mRNA expression level of PPARαin myocardial tissue of young and old patients increased significantly after ischemia-reperfusion injury,and the proportion of PPARαmRNA expression in young myocardial tissue was significantly higher than that in the elderly(P<0.05).The content of PPARαprotein in myocardial tissue of young and old patients increased significantly after ischemia-reperfusion injury,but the increase rate of PPARαprotein in young patients’myocardium was not significantly different from that in the elderly(P<0.05).Conclusion PPARαgene content and protein expression significantly decrease in human cardiomyocytes with increasing age.When suffering ischemia-reperfusion injury,PPARαgene content and protein expression significantly increase both in young and elderly cardiomyocytes,and the increase in PPARαof young heart may be more pronounced in older adults than in older adults.