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目的:研究H3K9me3在高糖诱导大鼠胸主动脉平滑肌A7r5细胞增殖中的作用,并初步探讨其可能的作用机制。方法:应用MTT法检测高糖刺激下不同浓度的H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin(0、10、25、50、75、100 nmol/L)和50nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在不同时间点(24、48、72 h和5 d)对细胞增殖的影响。应用Western bolt法观察50 nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在高糖浓度下干预A7r5细胞72 h后,对H3K9me3和p53表达的影响。结果:Chaetocin可显著抑制高糖诱导下A7r5细胞的增殖,且抑制作用呈浓度和时间依赖性。与正常糖相比,Chaetocin可显著下调A7r5细胞在高糖诱导下表达增多的H3K9me3,同时显著上调在高糖诱导下表达减少的p53(P<0.05)。结论:高糖可通过H3K9me3下调p53的表达促进大鼠胸主动脉平滑肌A7r5细胞的增殖,H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin可抑制上述过程,为减少糖尿病大血管并发症提供了治疗的新思路。
AIM: To investigate the role of H3K9me3 in the proliferation of rat aorta smooth muscle A7r5 cells induced by high glucose and to explore its possible mechanism. Methods: MTT assay was used to detect the effects of different concentrations of SUV39H1 specific inhibitor Chaetocin (0,10,25,50,75,100 nmol / L) and 50 nmol / L H3K9 methyltransferase SUV39H1 The specific inhibitor Chaetocin at different time points (24,48,72 h and 5 d) on cell proliferation. Western blot was used to observe the effect of 50 nmol / L H3K9 methyltransferase SUV39H1 specific inhibitor Chaetocin on the expression of H3K9me3 and p53 in A7r5 cells exposed to high glucose for 72 h. Results: Chaetocin significantly inhibited the proliferation of A7r5 cells induced by high glucose, and its inhibitory effect was concentration-dependent and time-dependent. Compared with normal sugar, Chaetocin significantly down-regulated H3K9me3 expression in A7r5 cells induced by high glucose, and significantly up-regulated p53 expression (P <0.05) under high glucose. CONCLUSION: High glucose can promote the proliferation of A7r5 cells in thoracic aorta by downregulating the expression of H3K9me3. Chaetocin, a specific inhibitor of H3K9 methyltransferase SUV39H1, can inhibit the above process and provide a therapeutic approach to reduce macrovascular complications of diabetes New ideas.