摘要
目的探讨二甲双胍对百草枯诱导的心肌细胞衰老的影响及可能机制。方法建立百草枯诱导心肌细胞衰老模型,根据衰老相关β-半乳糖苷酶(SA-β-Gal)染色阳性率和活性氧(ROS)水平评估二甲双胍对衰老心肌细胞的影响,采用RNA干扰技术抑制腺苷酸活化蛋白激酶(AMPK)表达,检测衰老相关指标及AMPK、沉默信息调节剂2相关酶1(Sirt1)蛋白含量的变化进一步探讨二甲双胍处理效应产生的可能机制。结果经百草枯干预后,细胞衰老阳性率增加,ROS表达增高,AMPK及Sirt1表达均明显减少,差异有统计学意义(P<0.05);与百草枯组比较,0.1 mmol/L二甲双胍干预组SA-β-Gal染色阳性细胞比例及ROS水平表达显著下降,AMPK及Sirt1蛋白表达增加,差异有统计学意义(P<0.05)。与二甲双胍干预组比较,二甲双胍联合AMPK siRNA干预组Sirt1表达减少,SA-β-Gal染色阳性细胞比例与ROS水平上升,差异有统计学意义(P<0.05)。结论二甲双胍能延缓百草枯诱导的心肌细胞衰老,其保护效应产生的机制可能与上调AMPK、增加Sirt1表达相关。
Objective To explore the effect of metformin on paraquat-induced myocardial cell senescence and its possible mechanism.Methods The model of paraquat-induced myocardial cell senescence was established.The levels of senescence-associatedβ-galactosidase(SA-β-Gal)staining positive rate and reactive oxygen species(ROS)were used to evaluate the effect of metformin on aging cardiomyocytes,and RNA interference was used to inhibit the expression of the adenosine 5’-monophosphate-activated protein kinase(AMPK),detect the changes of aging-related indicators and AMPK,sirtuin1(Sirt1)protein content,and further explore the possible mechanism of metformin treatment effect.Results After paraquat intervention,the positive rate of cell senescence increased,the expression of ROS increased,and the expressions of AMPK and Sirt1 decreased significantly,with statistically significant differences(P<0.05).Compared with the paraquat group,the proportion of stained positive cells of SA-β-Gal and the expression of ROS levels significantly decreased in the 0.1 mmol/L metformin intervention group,while the expressions of AMPK and Sirt1 proteins increased,with statistically significant differences(P<0.05).Compared with the metformin intervention group,the expression of Sirt1 in the metformin combined with AMPK siRNA intervention group was reduced,and the proportion of stained positive cells of SA-β-Gal and ROS levels increased,with statistically significant differences(P<0.05).Conclusion Metformin can delay the myocardial cell senescence induced by the paraquat,and the mechanism of its protective effect may be related to the upregulation of AMPK and the increase of Sirt1 expression.
作者
余星
刘文炽
肖婧雯
张彦
YU Xing;LIU Wenchi;XIAO Jingwen;ZHANG Yan(Department of Cardiovascular Medicine,Affiliated Fuzhou First Hospital of Fujian Medical University,Fujian,Fuzhou 350004,China;Department of Trauma Surgery,the First Affiliated Hospital of Fujian Medical University,Fujian,Fuzhou 350004,China)
出处
《中国医药科学》
2023年第23期17-20,共4页
China Medicine And Pharmacy
基金
福州市科技计划项目(2021-S-187)。
作者简介
通讯作者:张彦。
