基础医学与临床 ›› 2021, Vol. 41 ›› Issue (3): 364-369.

• 研究论文 • 上一篇    下一篇

过表达c-SKI抑制异丙肾上腺素诱导的小鼠心肌纤维化

张颖,向燕,张岳,王娟   

  1. 新疆医科大学第五附属医院
  • 收稿日期:2020-04-06 修回日期:2020-06-28 出版日期:2021-03-05 发布日期:2021-03-01
  • 通讯作者: 王娟 E-mail:15160991696@163.com
  • 基金资助:
    自治区自然科学基金

Over-expression of c-SKI inhibits isoprenaline-induced myocardial fibrosis in mice

  • Received:2020-04-06 Revised:2020-06-28 Online:2021-03-05 Published:2021-03-01
  • Contact: juan WANG E-mail:15160991696@163.com

摘要: 目的:探讨原癌基因c-SKI在异丙肾上腺素诱导的小鼠心肌纤维化中的作用及机制。方法:将小鼠分为对照组(Control组)、模型组(Model组)、c-SKI基因感染模型组(LV-SKI组)及对照病毒感染模型组(LV-NC组),每组10只。模型组采用皮下注射异丙肾上腺素(ISO)30 d,首次剂量为5 mg/kg后续以2.5 mg/kg。LV-SKI组和LV-NC组于18、21、24、27和30 d分别尾静脉注射c-SKI慢病毒和对照病毒,剂量均为100μL,滴度1×108 TU。HE染色和Masson染色观察心肌组织病理学,ELISA检测心肌组织中I型和III型胶原蛋白含量,Western blot检测c-SKI、间质细胞标志物波形蛋白(vimentin)、α-SMA、内皮细胞标志物CD31以及转录因子Snail、Twist及Slug的表达。结果:与对照组相比,模型组小鼠心肌纤组织中c-SKI的表达呈时间依赖性下降(P<0.01),模型组心肌细胞排列紊乱,间质显著增多,I型和III型胶原蛋白含量增加(P<0.01),心肌组织vimentin、α-SMA、Snail、Twist及Slug表达均上调,CD31蛋白表达下调(P<0.05)。过表达c-SKI后,与LV-NC组比较,小鼠心肌结构趋于整齐,间质胶原纤维减少,心肌组织中I型和III型胶原蛋白减少(P<0.01),vimentin、α-SMA蛋白的表达下调(P<0.05),CD31蛋白的表达上调(P<0.05),同时转录因子Snail、Twist和Slug蛋白的表达也随之下调(P<0.01)。结论:小鼠心肌纤维化进程中c-SKI表达下调,而过表达c-SKI能够通过抑制内皮-间充质转化改善异丙肾上腺素诱导的心肌纤维化。

关键词: 关键词 c-SKI, 心肌纤维化, 内皮-间充质转化, 转录因子

Abstract: Objective To investigate the effect of c-SKI on isoproterenol-induced cardiac fibrosis in Mice. Methods Mice were divided into 4 groups: the control group,the Model group,the c-SKI gene infection group (LV-SKI group) and the normal control virus infection group (LV-NC group), with 10 ones in each.In the model group, isoproterenol (ISO) was injected subcutaneously for 30d, with the first dose of 5 mg/kg followed by 2.5 mg/kg. In the LV-SKI group and the LV-NC group, c-SKI lentivirus and control virus were injected into the tail vein on days 18, 21, 24, 27 and 30 at a dose of 100μL, titer was 1×108 TU.HE staining and Masson staining were used to observe the pathological changes of myocardial tissue. ELISA was used to detect type I and type III collagen in myocardial tissue.Western blot was used to detect the expression of c-SKI,interstitial cell marker vimentin, α SMA,endothelial cell marker CD31 and the expression levels of transcription factors Snail, Twist and Slug. Results Compared with the control group, the expression of c-ski in the model group was time-dependent (P < 0.01). In the model group, the myocardial cells were disordered, the interstitium was significantly increased, and the contents of type I and type III collagen were increased (P < 0.01). Expressions of vimentin, α-SMA, Snail, Twist and Slug were all upregulated, while CD31 protein expression was down-regulated (P < 0.05). After over-expressing c-SKI, compared with the LV-NC group, the myocardial structure of the mice tended to be neat, the interstitial collagen fibers decreased, and the type I and III collagen in the myocardial tissue decreased (P < 0.01). The expression of vimentin and belt-sma was down-regulated (P < 0.05), and the expression of CD31 was up-regulated (P < 0.05). Meanwhile, the expression of transcription factors Snail, Twist and Slug was also down-regulated (P < 0.01). Conclusions c-SKI expression is down-regulated during myocardial fibrosis in mice, and overexpression of c-SKI can improve isoproterenol-induced myocardial fibrosis by inhibiting endothelial-mesenchymal transition.

Key words: Key words:c-SKI, cardiac fibrosis, End-MT, transcription factor