缬沙坦对博来霉素致大鼠肺纤维化的影响及机制  

Effects of valsartan on bleomycin-induced pulmonary fibrosis in rats and its mechanisms

作　　者：赵海山[1] 姚维凡[1] 魏敏杰[1] 

机构地区：[1]中国医科大学药学院,110001

出　　处：《山西医药杂志（上半月）》2013年第9期992-994,共3页Shanxi Medical Journal

摘　　要：目的探讨缬沙坦对博来霉素致大鼠肺纤维化的影响及可能机制。方法 Wistar大鼠随机分为对照组、模型组、缬沙坦低剂量组、缬沙坦高剂量组。气管内注入博莱霉素制备大鼠肺纤维化模型,当日灌胃缬沙坦,第7天、第14天、第28天分别处死大鼠。苏木素-伊红(HE)染色观察肺泡炎和肺纤维化程度,碱水解法检测肺组织羟脯氨酸(Hyp)浓度评价大鼠肺纤维化程度,化学比色法检测肺组织中超氧化物歧化酶(SOD)活力及丙二醛(MDA)水平,蛋白印迹法检测肺组织中转化生长因子(TGF)-β1、Smad2、E-钙黏附素(E-cadherin)及波形蛋白(vimentin)的表达。结果与模型组比较,缬沙坦2个剂量组大鼠肺纤维化程度显著减轻,肺组织Hyp含量显著减少,SOD活力明显增加,MDA水平明显减少,TGF-β1、Smad2、vimentin蛋白表达显著减少,E-cadherin蛋白表达显著增加(P<0.05),且有剂量依赖性。结论缬沙坦可减轻博莱霉素诱导的大鼠肺纤维化程度,其机制可能与其纠正氧化/抗氧化失衡,调节TGF-β1、Smad2、E-cadherin和vimentin蛋白表达有关。Objective To observe the effect of valsartan on bleomycin-induced pulmonary fibrosis in rats and to investigate the possible mechanism. Methods Wistar rats were randomly divided into control group, model group, low dose valsartan group and high dose valsartan group. Rat pulmonary fibrosis animal model was induced by intratracheal injection of bleomycin. Valsartan was delivered by intragastric administration daily. Rats were sacrificed on seventh day, fourth day and twenty-eighth day respectively. Pathology of alveolitis and pulmonary fibrosis was observed by HE staining and hydroxyproline （Hyp） content of pulmonary tissue was detected by alkaline hydrolysis method. The expression of TGF-β1, Smad2, vimentin and E-cadherin were detected by western blotting assay, activity of SOD and level of MDA were detected by Colourimetry. Results Valsartan dose-depend- ently reduced Hyp content of pulmonary tissue, attenuated alveolitis and pulmonary fibrosis, increased the SOD activity while reduced MDA level and increased the expression of E-cadherin protein while reduced the expression of TGF-β1, Smad2 and vimentin protein in lung tissue. Conclusion Valsartan could attenuate bleomycin--induced pulmonary fibrosis in rats, the possible mechanism is related to its effect of regulating the balance between oxidation and antioxidation and its effect of increasing the expression of E-eadherin protein and reducing the expression of TGF-β1, Smad2 and vimentin protein.

关 键 词：肺纤维化 博来霉素 缬沙坦 

分 类 号：R965[医药卫生—药理学]