衰老心肌自噬减退的新机制-转录因子EB的关键作用  

New mechanism of age-related myocardial autophagy decline: Key role of transcription factor EB

作　　者：张乐[1] 刘敏[1] 马颖[1] 胡建华[1] 纪兆乐 马恒[2] 李妍[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032 [2]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《心脏杂志》2015年第5期497-500,共4页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81170184;81170108;81322004)

摘　　要：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。AIM To explore the role of transcription factor EB （TFEB） in myocardial autophagic decline with aging. METHODS Age-related autophagic and TFEB changes in male C57BL/6 young （4 mo） and aged （22 mo） mice were analyzed. RESULTS Compared with young hearts, the aged heart had a lower level of autophagy （P 〈0. 05）. The autophagic markers including AtgS, LC3, Beclin-1 and lysosomal maker LAMP1 decreased in both protein and gene in the aged heart （ P 〈 0. 05 ）. In addi- tion, cardiomyocyte TFEB, especially in cardiomyocyte nuclei, was signifieantly reduced in the aged heart （P 〈 0. 05 ）, demonstrating that transcriptional activity of eardiomyocyte TFEB declined with aging. Systemic treatment with rapamycin in aged heart partly improved cardiomyocyte nuclear TFEB and auto- phagy as evidenced by increased autophagosome LC3-II level and increased lysosome LAMPI level （P 〈 0. 05）. CONCLUSION We demonstrate that age-related myocardial TFEB decreases significantly affects cardiomyocyte autophagy. TFEB is the key regulatory point of aging-associated myocardial autophagy decline.

关 键 词：衰老 心肌损伤 自噬 转录因子EB 

分 类 号：R392.3[医药卫生—免疫学]