曲美他嗪通过mTOR信号介导的自噬对大鼠心肌细胞损伤的作用  

Effect of Trimetazidine on Cardiomyocyte Injury of Rats through Autophagy Mediated by mTOR Signal

作　　者：李晓丽[1] 王洪江 池洪杰[1] LI Xiao-li;WANG Hong-jiang;CHI Hong-jie(Department of Cardiology,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院心内科,北京100020

出　　处：《解放军医药杂志》2022年第5期1-5,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：北京市卫生系统高层次卫生技术人才学科骨干基金(2015-3-028)。

摘　　要：目的探讨曲美他嗪(TMZ)通过mTOR信号通路抑制过度自噬对大鼠心肌细胞损伤的作用。方法利用乳鼠原代心肌细胞构建心肌细胞损伤模型。按照不同处理方法将细胞分为对照组(Control组)、模型组(Model组)、Model+TMZ组、Model+西罗莫司(RAPA)组、Model+TMZ+RAPA组。检测各组细胞凋亡情况、乳酸脱氢酶(LDH)和超氧化物歧化酶(SOD)水平,观察各组自噬小体及自噬流,并检测LC3-Ⅰ/Ⅱ、P62、Bax、Bcl-2、Caspase-3及mTOR蛋白表达水平。结果Model组细胞凋亡率、LDH、LC3-Ⅰ/Ⅱ、Bax、Caspase-3水平高于Control组,Model+TMZ组低于Model组,Model+RAPA组和Model+TMZ+RAPA组高于Model+TMZ组(P<0.05);Model组SOD、P62、Bcl-2、mTOR水平低于Control组,Model+TMZ组高于Model组,Model+RAPA组和Model+TMZ+RAPA组低于Model+TMZ组(P<0.05)。Model组心肌细胞自噬荧光积累,自噬流增加,加入TMZ后抑制受损心肌细胞中的自噬流,自噬小体数量减少,RAPA可部分抵消TMZ抑制自噬的作用。结论TMZ可能通过激活mTOR通路抑制过度自噬,减轻心肌细胞损伤及凋亡。Objective To explore the effect of Trimetazidine(TMZ)on cardiomyocyte injury of rats by inhibiting excessive autophagy through the mTOR signaling pathway.Methods The cardiomyocyte injury model was constructed using primary cardiomyocytes of neonatal rats.According to different treatments,the cells were divided into control group(Control group),model group(Model group),Model+TMZ group,Model+blocker rapamycin(RAPA)group,and Model+TMZ+RAPA group.The apoptosis,lactate dehydrogenase(LDH)and superoxide dismutase(SOD)levels were detected,and autophagosomes and fluorescence of each group were observed.The protein expression levels of LC3-Ⅰ/Ⅱ,P62,Bax,Bcl-2,Caspase-3 and mTOR were detected.Results The cell apoptosis rate,and the levels of LDH,LC3-Ⅰ/Ⅱ,Bax and Caspase-3 in the Model group were higher than those in the Control group,and the above indicators in the Model+TMZ group were lower than those in the Model group,and higher in Model+RAPA and Model+TMZ+RAPA groups than those in Model+TMZ group(P<0.05).The levels of SOD,P62,Bcl-2 and mTOR in the Model group were lower than those in the Control group,higher in Model+TMZ group than in the Model group,and lower in Model+RAPA and Model+TMZ+RAPA groups than those in Model+TMZ group(P<0.05).There was autophagy fluorescence accumulation of cardiomyocytes in the Model group and the increase of autophagy flux.After adding TMZ,the autophagy flux in the damaged cardiomyocytes was inhibited,and the number of autophagosomes decreased.RAPA could partially offset the effect of TMZ in inhibiting autophagy.Conclusion TMZ may inhibit excessive autophagy by activating the mTOR pathway,and reduce the damage and apoptosis of cardiomyocytes.

关 键 词：曲美他嗪 西罗莫司 细胞凋亡 乳酸脱氢酶 自噬 肌细胞 心脏 大鼠 Sprague-Dawley 

分 类 号：R-332[医药卫生] R542.22