转化生长因子-β1和阿托伐他汀对人心房成纤维细胞Ⅰ型胶原和Smads蛋白表达的影响  被引量:6

Effects of Transforming Growth Factor-β1 and Atorvastatin on the Expression of Collagen Type I P-Smads in Human Atrial Fibroblasts

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作  者:程显禄[1] 黄琦磊[1] 张建成[2] 

机构地区:[1]福建医科大学附属南平第一医院心内科,福建省南平市353000 [2]福建医科大学省立临床学院

出  处:《中国循环杂志》2015年第6期562-566,共5页Chinese Circulation Journal

摘  要:目的 :通过转化生长因子-β1(TGF-β1)和阿托伐他汀对培养的人心房成纤维细胞进行干预,观察其Ⅰ型胶原,Smad2、Smad4和Smad7 m RNA及蛋白表达的变化,探讨心房纤维化和抗纤维化机制。方法 :通过心外科手术获得患者右心耳组织,并培养出人心房成纤维细胞;将细胞传代培养,应用四唑盐比色(MTT)法检测不同浓度(0、0.1、1.0、5.0、10.0、20.0、50.0 ng/ml)TGF-β1和不同浓度(0、0.1、1.0、10.0、100.0μmol/L)阿托伐他汀对心房成纤维细胞生长影响;应用逆转录—聚合酶链反应(RT-PCR)和蛋白免疫印迹杂交(Western blot)技术检测10.0 ng/ml TGF-β1、10.0μmol/L阿托伐他汀以及10.0 ng/ml TGF-β1+10.0μmol/L阿托伐他汀联合对心房成纤维细胞中Ⅰ型胶原,P-Smad2,Smad4和Smad7 m RNA和蛋白表达的变化。结果:MTT法检测示:与对照(0 ng/ml)比,1.0 ng/ml和10.0 ng/ml TGF-β1干预使心房成纤维细胞Ⅰ型胶原、P-Smad2、Smad4的m RNA和蛋白表达水平增高(P<0.05),而Smad7的m RNA和蛋白表达水平减低(P<0.05),差异均有统计学意义;与10.0 ng/ml TGF-β1相比,TGF-β1加用或单用阿托伐他汀(10.0μmol/L)心房成纤维细胞Ⅰ型胶原、P-Smad2、Smad4的m RNA和蛋白表达水平减低(P<0.05),而Smad7 m RNA和蛋白表达水平增高(P<0.05),差异均有统计学意义。结论:TGF-β1促进心房成纤维细胞增殖和Ⅰ型胶原表达,阿托伐他汀抑制其增殖和Ⅰ型胶原表达,可能是通过影响TGF-β1/Smads途径起作用。Objective: To observe the effects of transforming growth factor-β1 (TGF-β1) and atorvastatin on expressions of collagen type I P-Smad2, Smad4 and Smad7 in human atrial ifbroblasts, and to explore the ifbrosis and anti-ifbrosis mechanisms in human atrium. Methods: Human right atrial appendage tissue was obtained from the cardiac surgery in our hospital and the atrial ifbroblasts were isolated and cultured by generations. The effects of TGF-β1 and atorvastatin on atrial ifbroblast proliferation was detected by MTT method and the effect of TGF-β1 at (0, 0.1, 1.0, 5.0, 10.0, 20.0, 50.0) ng/ml and atorvastatin at (0, 0.1, 1.0, 10.0, 100.0) μmol/L on mRNA and protein expressions of collagen type I P-Smad2, Smad4 and Smad7 in atrial ifbroblasts were examined by RT-PCR and Western-blotting analysis respectively. Results: MTT detection presented that compared to TGF-β1 at 0 ng/ml, with the intervention of TGF-β1 at (1 and 10) ng/ml, the mRNA and protein expressions of collagen type I P-Smad2, Smad4 increased,P〈0.05 and the expressions of Smad7 decreased,P〈0.05. Compared to TGF-β1 at 10.0 ng/ml, with the intervention of TGF-β1 + atorvastatin at 10.0 μmol/L or with atorvastatin at 10.0 μmol/L alone, the mRNA and protein expressions of collagen type I P-Smad2, Smad4 decreased,P〈0.05and expressions of Smad7 increased,P〈0.05. Conclusion: TGF-β1 promotes human atrial ifbroblast proliferation and collagen type I expression, while atorvastatin inhibits such proliferation and expression, the effect might be done by affecting TGF-β1/Smads pathway in human atrial ifbroblasts.

关 键 词:心血管病学 心房颤动 心房成纤维细胞 转化生长因子-Β1 SMADS蛋白 阿托伐他汀 

分 类 号:R54[医药卫生—心血管疾病]

 

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