摘要
目的探讨钙调神经磷酸酶(CaN)在心肌纤维化中的作用及阿托伐他汀(Ato)抗心肌纤维化的机制。方法采用体外新生SD大鼠心肌成纤维细胞(CFs)培养,以醛固酮(Ald)诱导其增殖和胶原合成,并加入Ato干预,应用RT-PCR和Westernblot分别测定CaNmRNA和蛋白表达,并观察加入焦磷酸法尼酯(FPP)和焦磷酸牛儿基牛儿酯(GGPP)分别干预Ato对RAS和RHO蛋白的抑制作用。结果Ald促进CFs增殖和增加羟脯氨酸含量,同时CaNmRNA和蛋白表达均升高,而Ato显著缓解上述变化。Ald+Ato+FPP组的CaNmRNA和蛋白表达均高于Ald+Ato组。结论Ato可通过CaN依赖的信号通路抑制Ald诱导的心肌纤维化,其作用与Ato通过甲羟戊酸通路抑制RAS蛋白活性有关。
Objective To investigate the roles of calcineurin （CaN） on cardiac fibrosis and to explore the effects of atorvastatin（Ato） on the expression of CaN. Methods Cardiac fibroblasts （CFs） of neonatal Sprague-Dawley rats were treated with aldosterone （Aid）, Ato, farnesyl pyrophosphate （FPP） and geranylgeranyl pyrophosphate （GGPP） respectively, CaN mRNA and protein were examined by RT-PCR and Western blot. Results Aid group significantly increased the proliferation of CFs, hydroxyproline concentration, the expression of CaN mRNA and protein. The increased expression of CaN mRNA and protein was negatively controlled by Ato. Compared with Aid ＋ Ato group, CaN mRNA and protein were up-regulated in Aid ＋ Ato ＋ FPP group. Conclusion Ato may decrease the expression of CaN by inhibiting RAS activity, which might result in the reversion of cardiac fibrosis induced by Aid.
出处
《基础医学与临床》
CSCD
北大核心
2007年第11期1281-1284,共4页
Basic and Clinical Medicine
