培哚普利对实验性肝纤维化大鼠TGF-β1及其Smad3、7的影响  

Effect of Perindopril on the Expression of TGF-β1, Smad3 and Smad7 in Experimental Hepatic Fibrosis in Rats

作　　者：龚作炯[1] 宋仕玲[1] 黄砚青[1] 王雪芬[1] 阮鹏[1] 

机构地区：[1]武汉大学人民医院感染科,430060

出　　处：《天津医药》2005年第9期579-581,共3页Tianjin Medical Journal

摘　　要：目的:探讨培哚普利抗大鼠肝纤维化的疗效及作用机制。方法:用培哚普利治疗四氯化碳诱导大鼠肝纤维化模型。免疫组化技术检测TGF-β1、Smad3及Smad7在肝内的表达及定位,常规生化方法检测肝功能,放射免疫方法检测透明质酸(HA),肝组织VanGiseonr染色、HE染色。结果:经培哚普利治疗后大鼠肝组织内TGF-β1及Smad3表达降低,而Smad7的表达增加。TGF-β1及Smad3的免疫阳性反应信号主要位于纤维间隔中的细胞浆,Smad7则主要在肝细胞浆表达。血清谷氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、HA显著减低,肝小叶结构趋于正常,纤维间隔明显变薄。结论:培哚普利能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度,与其抑制肝内TGF-β1及Smad3,促进Smad7表达有关。Objective： To investigate the effects and mechanisms of Perindopril on liver fibrosis rats. Methods：Perindopril was used to treat rat liver fibrosis model induced by carbon tetra chloride. The effect of Perindopril was explored by the expressions and sites of transforming growth factor-betal （TGF-β1）, Smad3 and Smad7 in liver tissues by immunohistochemical staining. The liver function, serum hyalauronic acid （HA）, liver histopathology were also examined by biochemsitry, RIA, HE and Van Gieson stainings respectively. Results： The expressions of TGF-β1 and Smad3 of rats that received Perindopril were significantly decreased, however the expression of Smad7 was also obviously increased in the livers, The immunity-positive signal of TGF-β1 and Smad3 was mostly located in cytoplasm of fiberinterval and expression of Smad7 was mostly located in hepatic cells.The level of serum ALT and AST HA were markedly decreased, meanwhile, the construction of the liver almost obtained the normal level and fiberinterval became thin. Conclusion： The Perindopril has protective effects on liver injury and can inhibit liver fibrosis in rats. The mechanisms are possibly associated with its effect of down-regulating TGF-β1 and smad3, up-regulating Smad7 and result in suppressing the activation of hepatic cells.

关 键 词：培哚普利 实验性肝纤维化 大鼠 TGF-β1 SMAD3 SMAD7 药物治疗 肝脏损伤 

分 类 号：R575.2[医药卫生—消化系统] R975[医药卫生—内科学]