过氧化体增殖物激活型受体γ抑制转化生长因子β1诱导的血管平滑肌细胞钙化  

Peroxisome proliferator-activated receptorγ inhibits TGF-β1-induced calcification of vascular smooth muscle cells

作　　者：王亚萍 何胜虎 WANG Yaping;HE Shenghu(Department of Cardiology,Northern Jiangsu People's Hospital,Yangzhou,Jiangsu 225001,China)

机构地区：[1]扬州大学临床医学院江苏省苏北人民医院心内科

出　　处：《中国动脉硬化杂志》2018年第12期1206-1211,共6页Chinese Journal of Arteriosclerosis

摘　　要：目的探讨过氧化体增殖物激活型受体γ(PPARγ)对转化生长因子β1(TGF-β1)诱导的大鼠主动脉血管平滑肌细胞(VSMC)钙化的作用。方法体外培养大鼠主动脉VSMC,先分为正常对照组、不同浓度TGF-β1组(1、2、4、8μg/L),观察TGF-β1对VSMC的影响;再分为正常对照组、钙化组(TGF-β14μg/L)、罗格列酮(RSG,20μmol/L)组、钙化+罗格列酮(RSG,20μmol/L)组,观察PPARγ激动剂罗格列酮对VSMC钙化后的作用,对细胞进行钙含量和碱性磷酸酶(ALP)活性检测,茜素红S染色检测钙化结节的形成情况,Western blot检测VSMC标志物α平滑肌肌动蛋白(α-SMA)、PPARγ、成骨样细胞标志物Runt相关转录因子2(Runx2)的蛋白表达情况。结果与正常对照组相比,TGF-β1处理后的VSMC钙盐沉积和ALP活性明显升高(P<0.05),且TGF-β1浓度为4μg/L时作用最明显,成骨样细胞标志物Runx2表达明显升高(P<0.05),同时平滑肌细胞标志物α-SMA表达减少(P<0.05)。而加入罗格列酮后,VSMC的钙盐沉积和ALP活性明显降低(P<0.05),α-SMA、PPARγ表达明显上升(P<0.05),相反,Runx2的表达则明显受到抑制(P<0.05)。结论TGF-β1可以诱导VSMC向成骨样细胞分化和钙化,而PPARγ激动剂罗格列酮可以抑制TGF-β1诱导下VSMC钙化的发生。Aim To investigate the effect of peroxisome proliferators activated receptorγ ( PPARγ) on the calcification of rat aortic vascular smooth muscle cells ( VSMC) induced by transforming growth factor-β1 ( TGF-β1) . Methods Rat aortic vascular smooth muscle cells were cultured in vitro and divided into normal control group and different concentrations of TGF-β1 group ( 1 μg /L,2 μg /L,4 μg /L,8 μg /L) . Then they were divided into normal control group,calcification group ( TGF-β1 4 μg /L) ,rosiglitazone group ( RSG,20 μmol /L) ,and calcification+rosiglitazone ( RSG,20 μmol /L) group. The effects of agonist RSG on calcification of VSMC,calcium content and alkaline phosphatase ( ALP) activity were detected in the cells,alizarin red S staining was used to detect the formation of calcified nodules, and Western blot was used to detect vascular smooth muscle cells marker α-smooth muscle actin ( α-SMA) ,PPARγ,protein expression of osteoblast-like marker Runt-related transcription factor ( Runx2) . Results Compared with the normal control group,calcium deposition and ALP activity of VSMC treated with TGF-β1 were significantly increased ( P< 0.05) ,and the effect was most obvious when TGF-β1 concentration was 4 μg /L. And Runx2 expression of osteoblast-like cell was significantly increased ( P< 0.05) ,while α-SMA expression of smooth muscle cell markers was decreased ( P< 0.05) . Whereas calcium sulfate deposition and ALP activity of VSMC were significantly decreased ( P<0.05) ,α-SMA and PPARγ expression was significantly increased after RSG was added( P<0.05) ,on the contrary,Runx2 expression was sig-nificantly inhibited ( P<0.05) . Conclusion TGF-β1 can induce differentiation and calcification of VSMC into osteoblast- like cells,and TGF-β1-induced calcification of VSMC can be inhibited by PPARγ agonist RSG.

关 键 词：血管平滑肌细胞 转化生长因子Β1 血管钙化 过氧化体增殖物激活型受体Γ 

分 类 号：R54[医药卫生—心血管疾病]