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目的探讨转录因子EB(TFEB)在衰老心肌自噬减退中的作用。方法采用老年(22月龄)雄性C57BL/6小鼠为实验对象,以成年(4月龄)雄性C57BL/6小鼠为对照,分析心肌自噬水平、心肌TFEB表达水平。结果与成年心肌相比,衰老心肌自噬水平显著降低(P<0.05)。衰老心肌中自噬体标志物Atg5、LC3和Beclin-1,溶酶体标志物LAMP1在蛋白和mRNA水平上均出现降低。与成年心肌相比,衰老心肌TFEB蛋白水平显著降低(P<0.05),衰老心肌细胞核内的TFEB水平下降更为显著(P<0.05),提示衰老心肌TFEB转录能力减退。给予小剂量雷帕霉素处理,可提高衰老心肌细胞核内TFEB水平,并且改善LC3及LAMP1的mRNA和蛋白水平,提高衰老心肌自噬水平。结论本研究发现衰老导致的心肌TFEB水平降低严重影响心肌自噬能力,提示TFEB是心肌自噬增龄性减退机制中的关键调节因子。
Objective To investigate the role of transcription factor EB (TFEB) in the decline of autophagy in senile myocardium. Methods Male C57BL / 6 mice (22 months old) were used as experimental subjects. The levels of autophagy and TFEB in male C57BL / 6 mice (4 months old) were compared. Results Compared with adult myocardium, the level of autophagy in senescent myocardium decreased significantly (P <0.05). Autophagosome markers Atg5, LC3 and Beclin-1 in senescent myocardium, and LAMP1, a lysosome marker, both decreased in both protein and mRNA levels. Compared with adult myocardium, the level of TFEB in senescent myocardium decreased significantly (P <0.05), and the level of TFEB in senescent cardiomyocytes decreased more significantly (P <0.05). Small doses of rapamycin treatment can increase the level of TFEB in the nucleus of aged myocardial cells, and improve the mRNA and protein levels of LC3 and LAMP1 and increase the level of autophagy in aged myocardium. Conclusion The study found that the decrease of myocardial TFEB induced by aging seriously affected the autophagy ability, suggesting that TFEB is a key regulatory factor in the mechanism of myocardial autophagy.