阿齐沙坦对转化生长因子诱导的自发性高血压大鼠血管平滑肌细胞增殖及迁移的影响

Effects of Azilsartan on TGF-β Induced Spontaneously Hypertensive Vascular Smooth Muscle Cells Proliferation and Migration

目的探讨阿齐沙坦对转化生长因子-β（TGF-β）诱导的自发性高血压大鼠血管平滑肌细胞（VSMCs）增殖及迁移的影响。方法采用组织块贴壁培养法进行血管平滑肌细胞的原代培养,取3～5代细胞用于实验。用MTT法测定细胞增殖情况,用Boyden小室测试细胞迁移情况。采用10ng/ml TGF-β刺激VSMCs,并用阿齐沙坦干预,24h后用Western blot和RT-PCR检测VSMCs中MMP-2、MMP-9及TIMP-1蛋白和mRNA的表达。结果 TGF-β可促进大鼠VSMCs的增殖及迁移,并增加大鼠VSMCs的MMP-2、MMP-9和TIMP-1蛋白表达。阿齐沙坦则可抑制TGF-β诱导的大鼠VSMCs的增殖和迁移,并降低大鼠VSMCs的MMP-2、MMP-9及TIMP-1表达。结论阿齐沙坦可能通过下调MMP-2、MMP-9及TIMP-1的表达来抑制TGF-β诱导的自发性高血压血管平滑肌细胞的增殖及迁移。

Objective To investigate the effects of azilsartan on TGF-β-induced spontaneously hypertensive vascular smooth muscle cells（ VSMCs） proliferation and migration. Methods Rat VSMCs were cultivated by the method of tissue explants adherence. Cells of generation 3 to 5 were used as the experimental system. The MTT test was used to measure cell proliferation and Boyden chamber assay was used to measure cell migration. Primary cultured VSMCs were treated by 10 ng /ml TGF-β and azilsartan for 24 hours. The expression of MMP-2,MMP-9,TIMP-1 were measured by Western blot and RT-PCR. Results The expression of MMP-2,MMP-9 and TIMP-1 in rat VSMCs stimulated by TGF-β increased significantly. VSMCs migration and proliferation also increased significantly. Azilsartan significantly inhibited TGF-β induced MMP-2,MMP-9 and TIMP-1production in rat VSMCs,as well as VSMCs proliferation and migration. Conclusions Azilsartan inhibited TGF-β-induced VSMCs proliferation and migration by down-regulation the expression of MMP-2,MMP-9,TIMP-1.