姜黄素通过激活SIRT1抑制AngⅡ诱导的心肌纤维化

Curcumin inhibited AngⅡ-induced cardiac fibrosis by activating SIRT1

目的研究姜黄素(Curcumin)对血管紧张素Ⅱ(AngⅡ)诱导的心肌纤维化的影响,并观察其对SIRT1的调控。方法心肌成纤维细胞给予Curcumin预处理后再给予AngⅡ刺激,采用Cell Counting Kit-8(CCK-8)法检测成纤维细胞增殖水平,羟脯氨酸检测试剂盒检测成纤维细胞中羟脯氨酸的水平,Real-time PCR法检测collagen-Ⅰ、collagen-Ⅲ、CTGF、FN等基因mRNA表达变化,Western Blotting和SIRT1酶活性检测试剂盒分别检测沉默信息调节因子1(silent information regulator 1,SIRT1)的蛋白表达及去乙酰化酶活性的变化。结果给予AngⅡ处理24 h后,细胞增殖水平增加、胶原合成相关基因表达增多、纤维化相关基因CTGF、FN的mRNA表达显著增加,并且SIRT1的蛋白水平和去乙酰化酶活性显著下降;Curcumin预处理可明显抑制AngⅡ诱导的心肌成纤维细胞增殖,抑制胶原合成以及纤维化相关基因CTGF、FN的表达,并增加SIRT1的蛋白水平和酶活性。结论 Curcumin可抑制AngⅡ诱导的心肌细胞纤维化,其机制可能与SIRT1的激活有关。

Objective： To examine the effect of Curcumin on cardiac fibrosis induced by Ang Ⅱ,and elucidate the role of SIRT1. Methods： The cultured rat cardiac fibroblasts were preincubated with Curcumin for 1 h followed by treatment with100 nmol/L AngⅡ for 24 h. The cell proliferation was determined by cell counting kit-8（ CCK-8） assays,the mRNA expression levels of collagen-Ⅰ,collagen-Ⅲ,CTGF,FN were detected by Real-time PCR,the protein expression and enzyme activity of SIRT1 were detected by Western blotting and fluorometric assay Kit respectively. Results： Ang II-induced cardiac fibroblasts proliferation was inhibited by 20 μmol/L Curcumin. The mRNA expression of collagen-I,collagen-III,FN and CTGF were significantly upregulated by Ang II which could be attenuated by Curcumin pretreatment. Moreover,the protein expression and enzyme activity of SIRT1 were downregulated after Ang Ⅱ treatment,which could be reversed by Curcumin. Conclusion： Curcumin can inhibit AngⅡ-induced cardiac fibrosis by activating SIRT1.