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