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目的:探讨mi R-130a在血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)诱导心脏间质纤维化中的作用及分子机制。方法:埋植Ang Ⅱ微渗泵制备小鼠心室重塑模型,超声心动检测小鼠心功能;离体培养乳鼠心脏成纤维细胞,real-time PCR和Western blot检测分子的基因及蛋白表达。结果:在埋植Ang Ⅱ微渗泵的小鼠心肌组织以及Ang Ⅱ刺激的乳鼠心脏成纤维细胞,Ang Ⅱ可上调mi R-130a的表达。小鼠腹腔注射25 mg/kg mi R-130a抑制剂锁核酸(locked nucleic acid,LNA)-anti-mi R-130a可显著抑制Ang Ⅱ引起的心肌组织中mi R-130a表达增加,改善Ang Ⅱ引起心脏间质纤维化及舒缩功能障碍。转染mi R-130a mimic可进一步促进Ang Ⅱ引起的纤维化相关分子的表达增加以及肌成纤维细胞转化,mi R-130a inhibitor则可抑制Ang Ⅱ的上述作用。过表达PPAR-γ可抑制Ang Ⅱ以及Ang Ⅱ和mi R-130a mimic联合应用引起的纤维化相关分子的表达。结论:mi R-130a通过调控PPAR-γ的表达参与Ang Ⅱ的促纤维化效应。
Objective: To investigate the molecular mechanism of mi R-130a in cardiac interstitial fibrosis induced by angiotensin Ⅱ (Ang Ⅱ). Methods: Mouse ventricular remodeling was induced by implantation of Ang Ⅱ micro-osmotic pump. Cardiac function was detected by echocardiography. Cardiac fibroblasts were cultured in vitro. Real-time PCR and Western blot were used to detect the gene and protein expression. Results: Ang Ⅱ upregulated the expression of mi R-130a in the cardiac tissue of mice implanted with Ang Ⅱ micro-osmotic pump and in the cardiac fibroblasts of Ang II-stimulated neonatal rat hearts. Mouse intraperitoneal injection of 25 mg / kg mi R-130a locked nucleic acid (LNA) -anti-mi R-130a significantly reduced the expression of mi R-130a in myocardium induced by Ang Ⅱ, Cause cardiac interstitial fibrosis and systolic dysfunction. Transfection of mi R-130a mimic could further promote the expression of fibrosis related molecules induced by Ang Ⅱ and the transformation of myofibroblasts, and mi R-130a inhibitor could inhibit the above effects of Ang Ⅱ. Overexpression of PPAR-γ inhibited the expression of fibrosis-related molecules induced by Ang Ⅱ and Ang Ⅱ and mi R-130a mimic. Conclusion: mi R-130a is involved in the pro-fibrotic effect of Ang Ⅱ through regulating the expression of PPAR-γ.