替米沙坦对肝纤维化大鼠肝组织TGFβ1、PDGF和PPAR-γ表达的影响

The effect of telmisartan on TGFβ1,PDGF and PPAR-γ expression in hepatic tissues of rats with CCl4-induced hepatic fibrosis

目的研究替米沙坦抗肝纤维化的分子生物学机制。方法将40只SD大鼠随机分成正常组(12只)、模型组(12只)和替米沙坦干预组(16只)。在制备四氯化碳(CCl4)肝纤维化动物模型成功后,用免疫组化法测定肝组织转化生长因子β1(TGF-β1)、过氧化物酶体增生物活化受体-γ(PPAR-γ)及血小板源生长因子(PDGF)表达。结果替米沙坦干预组大鼠肝组织TGF-β1平均标记指数(PI)为0.284±0.068,正常对照组为0.076±0.033,均显著低于模型对照组(0.739±0.065,P<0.01);替米沙坦干预组大鼠PDGF PI为0.259±0.050,正常对照组为0.039±0.023,均显著低于模型对照组(0.511±0.107,P<0.01);替米沙坦干预组PPAR-γ平均PI为0.326±0.068,正常对照组为0.115±0.021,均显著高于模型对照组(0.038±0.018,P<0.01)。结论替米沙坦通过活化实验性肝纤维化大鼠肝组织PPAR-γ,抑制肝脏细胞因子表达,达到抗肝纤维化作用。

Objective To investigate the effect of telmisartan on TGFβ1 ,PDGF and PPAR-γ expression in hepatic tissues of rats with CCl4-induced hepatic fibrosis. Methods 40 rats were randomly divided into normal （n=12）,CCl4-induced hepatic fibrosis model（n=12） and telmisartan intervention group （ n=16 ）. TGF-β1, PPAR-γ and PDGF in liver tissues were detected by immunohistochemical assay. Results The TGF-β1 expression in telmisartan-treated group （painting index,PI=0.284±0.068,P〈0.01）was remarkably lower than in model group （PI=0.739±0.065）;A significant reduction of PDGF was also observed in telmisartan treated group （PI= 0.259±0.050,P〈0.01 ） than in model group （0.511 ±0.107） ;However,the PPAR-γ level in telmisartan treated group （PI=0.326±0.068,P〈0.01） was significantly higher than in model group （PI=0.038±0.018）. Conclusions Telmisartan exerts protective and therapeutic effects by reducing the levels of TGF-β1 and PDGF,but enhancing the activation of PPAR- γ in rats.