摘要
目的探讨抑制沉默信息调节因子1(SIRT1)/p53通路对同型半胱氨酸(Hcy)诱导的心肌纤维化的影响。方法体外培养心肌成纤维细胞(CF),分为NC组、Hcy组、EX527+Hcy组进行实验。NC组为正常培养的CF;Hcy组的CF给予0.5 mmol/L的Hcy刺激;EX527+Hcy组的CF在给予0.5 mmol/L的Hcy刺激后加入SIRT1/p53通路抑制剂EX527进行干预。干预结束后,检测各组细胞的增殖率、凋亡率,细胞中纤维化相关因子Ⅰ型胶原α1链(COL1A1)、Ⅲ型胶原α1链(COL3A1)和肌动蛋白α2(Acta2)的mRNA和蛋白表达水平,以及细胞中SIRT1/p53通路相关蛋白SIRT1、乙酰化p53(Ac-p53)的表达水平。结果(1)与NC组比较,Hcy组CF增殖率升高,凋亡率降低(均P<0.05);与Hcy组比较,EX527+Hcy组细胞增殖率降低,而凋亡率升高(均P<0.05)。(2)与NC组比较,Hcy组CF中COL1A1、COL3A1和Acta2的mRNA和蛋白相对表达水平均升高(均P<0.05);与Hcy组比较,EX527+Hcy组CF中COL1A1、COL3A1和Acta2的mRNA和蛋白相对表达水平均降低(均P<0.05)。(3)与NC组比较,Hcy组CF细胞中SIRT1蛋白相对表达水平升高,Ac-p53蛋白相对表达水平降低(均P<0.05);与Hcy组比较,EX527+Hcy组细胞中SIRT1蛋白相对表达水平降低,Ac-p53蛋白相对表达水平升高(均P<0.05)。结论抑制SIRT1/p53信号通路可促进Hcy诱导的CF凋亡,并抑制CF增殖,从而缓解Hcy诱导的心肌纤维化。
Objective To investigate the effect of inhibiting sirtuin 1(silent information regulator 1,SIRT1)/p53 pathway on myocardial fibrosis induced by homocysteine(Hcy).Methods Cardiac fibroblasts(CF)cultured in vitro were divided into NC group,Hcy group,EX527+Hcy group for the experiment.CF in the NC group were cultured normally,CF in the Hcy group were given stimulation with 0.5 mmol/L Hcy,CF in the EX527+Hcy group were given stimulation with 0.5 mmol/L Hcy prior to intervention with SIRT1/p53 pathway inhibitor EX527.After the end of intervention,detection was performed on the proliferation rate and apoptosis rate of CF,mRNA and protein expression levels of fibrosis-related factors collagen typeⅠalpha 1 chain(COL1A1),collagen typeⅢalpha 1 chain(COL3A1)and actin alpha 2(Acta2),as well as expression levels of SIRT1/p53 pathway-related proteins SIRT1 and acetylated p53(Ac-p53)in CF of all groups.Results(1)Compared with the NC group,the Hcy group had an elevated proliferation rate and a decreased apoptosis rate of CF(all P<0.05);compared with the Hcy group,the EX527+Hcy group exhibited a reduced proliferation rate and an increased apoptosis rate of the cells(all P<0.05).(2)The Hcy group yielded higher relative expression levels of COL1A1,COL3A1 and Acta2 mRNAs and proteins in CF in comparison with the NC group(all P<0.05);the relative expression levels of COL1A1,COL3A1 and Acta2 mRNAs and proteins in CF in the EX527+Hcy group were lower than those in the Hcy group(all P<0.05).(3)The relative expression level of SIRT1 protein in CF was higher and the relative expression level of Ac-p53 protein was lower in the Hcy group than in the NC group(all P<0.05);compared with the Hcy group,the EX527+Hcy group reported a decreased relative expression level of SIRT1 protein in the cells,and an elevated relative expression level of Ac-p53 protein(all P<0.05).Conclusion Inhibiting SIRT1/p53 signaling pathway can promote the Hcy-induced apoptosis of CF and inhibit the proliferation of CF,thus ameliorating Hcy-induced myocardial fibro
作者
余平
李叶子
万少兵
YU Ping;LI Ye-zi;WANG Shao-bing(Department of Emergency,Wuhai Third Hospital,Wuhai 430060,China)
出处
《广西医学》
CAS
2021年第19期2322-2326,共5页
Guangxi Medical Journal
基金
湖北省武汉市卫生和计划生育委员会科研课题(WX18D47)。
