中文摘要：

目的研究缬沙坦对血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）诱导的大鼠血管平滑肌细胞（vascular smooth mus-cle cells,VSMCs）增殖的影响,并探讨其新的作用机制。方法体外培养VSMCs,采用AngⅡ诱导其增殖,用不同浓度的缬沙坦（10-5、10-6、10-7 mol/L）进行干预,细胞计数及四氮唑盐试验（MTT）检测VSMCs增殖情况,Western blot检测各组线粒体融合素基因-2（mitofusin-2,Mfn2）、Raf、细胞外信号调节激酶1/2（extracellular signalregulated kinase 1/2,ERK1/2）表达水平的变化。结果 AngⅡ能够明显促进VSMCs的增殖,下调Mfn2的表达、增强Raf和ERK1/2的表达;缬沙坦10-5、10-6 mol/L可以拮抗AngⅡ的上述作用,而缬沙坦10-7 mol/L无此作用;缬沙坦对无AngⅡ刺激的VSMCs增殖无明显影响。结论缬沙坦能有效抑制AngⅡ诱导的VSMCs增殖,其机制与调节Mfn2的表达、抑制Ras-Raf-ERK/MAPK信号通路有关。

英文摘要：

Objective To study the inhibitory effect and new molecular mechanism of valsartan on cell proliferation induced by angiotensin Ⅱ（AngⅡ）in rat aortic vascular smooth muscle cells（VSMCs）.Methods VSMCs were cultured in vitro and stimulated with 10-6 mol/L AngⅡ,then interfered with valsartan at different concentrations（10-5,10-6,and 10-7 mol/L）.Cell counting and MTT assay were used to assess the proliferation and the viability of VSMCs.Western blot was used to detect the expression of Mfn2,Raf and ERK1/2 in cell proliferation signaling pathway.Results AngⅡ significantly promoted VSMCs proliferation,down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2 at the concentration of 10-6 mol/L.Valsartan inhibited those effects of AngⅡ at the concentration of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no influence on the proliferation of VSMCs without AngⅡ.Conclusion Valsartan can effectively inhibit the proliferation of VSMCs induced by AngⅡ in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.