转化生长因子β_1/Smads表达在高盐饮食致Wistar大鼠心肌纤维化中的作用及替米沙坦干预  

The expression of transforming growth factor-β_1/Smads signaling pathway in left ventricular myocardial fibrosis induced by high- salt diet in Wistar rats and the prevention of telmisartan

作　　者：李同[1,2] 商黔惠[1,2] 刘婵[1] 石耿辉[1] 

机构地区：[1]遵义医学院临床医学研究所 [2]遵义医学院附属医院心内科,贵州遵义563003

出　　处：《中华高血压杂志》2013年第7期648-653,共6页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助项目(81160041);贵州省社会发展攻关计划项目 黔科合SY字(2011)3047;省国际科技合作计划项目 黔科合外G字(2012)7038

摘　　要：目的探讨转化生长因子β1(TGF-β1)/Smads表达在高盐(8%NaCl)诱导Wistar大鼠左心室心肌纤维化中的作用及替米沙坦的干预效应。方法雄性Wistar大鼠49只随机分为对照组(n=13,饲0.5%NaCl),模型组(n=24,饲8%NaCl),干预组(n=12,饲8%NaCl+替米沙坦2mg/kg灌胃),喂养24周。每两周测一次尾动脉压。Masson染色观察左心室心肌纤维化程度。运用实时荧光定量聚合酶链反应技术检测左心室TGF-β1、Smad2、Smad3及Smad7的mRNA表达,同时采用免疫印迹法检测左心室α平滑肌肌动蛋白(α-SMA)、TGF-β1、磷酸化Smad2/3(P-smad2/3)、Smad7蛋白的表达。结果与对照组比较,模型组血压升高(P<0.05),左心室心肌间质、心肌内血管周围及血管壁胶原容积分数增大,α-SMA蛋白的表达水平升高(P<0.05);TGF-β1、Smad2、Smad3的mRNA与蛋白表达水平升高(均P<0.05),而Smad7的mRNA与蛋白的表达水平降低(均P<0.05)。与模型组比较,干预组血压降低(P<0.05),左心室心肌间质、心肌内血管周围及血管壁胶原容积分数减少[(7.94±0.93)%比(17.38±1.37)%;(17.88±5.97)%比(52.32±9.93)%,(21.26±6.83)%比(61.31±9.25)%;均P<0.05],α-SMA蛋白表达水平下调[(0.146±0.012)比(0.206±0.018),P<0.05];TGF-β1的蛋白表达水平下调[(0.035±0.005)比(0.084±0.010),P<0.05],Smad2、Smad3的mRNA表达量降低[Smad2(146.8±21.7)比(304.2±34.0);Smad3(139.2±15.1)比(354.1±52.4),均P<0.05],而Smad7的mRNA与蛋白表达水平均上调[分别(171.6±13.9)比(43.7±1.7);(0.607±0.115)比(0.298±0.045),均P<0.05]。结论长期高盐饮食可诱导Wistar大鼠血压升高及心肌纤维化,其机制与TGF-β1/Smads表达异常相关;替米沙坦抗高血压及左心室纤维化的作用可能部分是通过阻断血管紧张素Ⅱ1型受体影响TGF-β1/Smads表达实现的。Objective To investigate the effects of transforming growth factor （TGF-β1）/Smads signaling pathway and the preventive effects of telmisartan on the pathogenesis of salt-induced left ventricular fibrosis in Wistar rats. Methods Forty nine male Wistar rats were randomly assigned into three groups： normal control group （fed with 0.5% NaC1, n=13）, high-salt model group （fed with 8% NaC1, n=24）, and intervention group （fed with 8% NaCl＋telmisartan 2 mg/kg, n= 12）. All rats were fed for twenty-four weeks. Tail-cuff artery pressures were determined every two weeks. Collagen volume fractions （CVF） of left ventricle were observed by Masson staining. The mRNA and protein levels of TGF-β1 , Smad2, Smad3 and Smad7 were determined by real time fluorescent quan- titative reverse transcripatase polymerase chain reaction and left ventricular a-smooth muscle actin （a-SMA）, TGF-β1 , Smad2/3 and Smad7 were detected by Western blot. Results Compared with those of normal control group, the CVF of left ventrielar myocardium, perivascular and vascular wall was significantly higher in high-salt model group as same as blood pressure and protein level of ccSMA （all P%0.05）, and the mRNA and protein expressions of TGF-β1, Smad2, and Smad3 were also elevated [mRNA expression： TGF-β1 , Smad2, Smad3; protein expres sion. TGF-β1, P-smad2/3; alI P〈0.05], while these of Smad7 was decreased （all P〈0.05）. Compared with those of the high-salt model group, the CVF of left ventriclar myocardium, perivascular and vascular wail in interven- tion group was down regulated [（7.94±0.93）% vs （17.38±1.37）%; /17.88±5.97）% vs （52.32±9.93）%, （21.26±6.83）% vs （61.31±9.25）%; all P〈0.05], so did blood pressure, the protein level of TGF-β1 , a-SMA and the mRNA expression of Smad2 and Smad3 [α-SMA（0. 146±0. 012） vs （0. 206±0. 018）; TGF-β1 （0. 035±0. 005） vs （0. 084±0. 010） ; Smad2（146.8±21.7） vs （304. 2±34. 0）, Smad3（139.2±15.1） vs （354. 1±52.4）

关 键 词：转化生长因子β1 SMADS信号通路 高盐饮食 高血压 心肌纤维化 替米沙坦 WISTAR大鼠 

分 类 号：R965[医药卫生—药理学]