摘要目的 观察缬沙坦对急性肺损伤大鼠TGF-β/Smad信号通路的影响.方法 24只SD雄性大鼠随机分为对照组、模型组和缬沙坦组三组,每组8只.缬沙坦组于气管内滴注博莱霉素(BLM)生理盐水溶液(5 mg/kg)以复制急性肺损伤动物模型,并于造模当天每日给予缬沙坦(20mg/kg)灌胃;模型组以生理盐水代替缬沙坦灌胃;对照组则均用生理盐水代替BLM和缬沙坦.各组动物均于制模开始后第7天处死,分取肺组织行病理切片HE染色观察肺损伤程度、免疫组化技术检测肺组织TGF-β1、Smad2/3和Smad7蛋白的表达水平.结果 缬沙坦组大鼠肺组织损伤程度较模型组比较明显减少(P＜0.01).模型组肺组织内TGF-β1、Smad2/3蛋白表达水平较对照组明显增强(P＜0.01).缬沙坦组TGF-β1、Smad2/3蛋白表达水平较模型组降低(P＜0.01).Smad7蛋白在模型组肺组织内表达明显低于对照组(0.23±0.02 vs 0.36±0.03,P＜0.01),缬沙坦组Smad7蛋白表达同模型组比较明显增强(P＜0.01).结论 缬沙坦可下调急性肺损伤大鼠肺组织内TGF-β1、Smad2/3蛋白表达,上调Smacd7蛋白表达,从而阻断TGF-β/Smad信号通路,减轻急性肺损伤程度.

abstractsObjective To observe the effect of Valsartan on a rat model of acute lung injury and the expression of transforming growth factor-β,TGF-β) ,Smad2/3, Smad7. Methods Twenty-four male adult Sprague-Dawley rats were random divided into three groups : The bleomycin (BLM) group, the control group, and the Valsartan group. Each group contained eight rats. The Valsartan group was treated with Valsartan everyday at a dose of 20 mg/kg after a single intratracheal instillation of bleomycin at a dose of 5mg/kg. BLM group was treated with saline instead of Valsartan after an instillation of bleomycin. The control group was treated with saline instead of Valsartan and bleomycin. Each group was killed at the 7th day after instillation. The lung tissues were harvested for H. E. stain, the immunohistochemistry was used to detect the expressions of TGF-β1, Smad2/3 ,and Smad7. Results The degree of alveolitis in the Valsartan group was ameliorated, compared with those in BLM group (P ＜0. 01). The expressions of TGF-β1 and Smad2/3 in lung tissue of the Valsartan group were significantly lower than that of BLM group(P ＜0. 01). The expressions of Smad7 in lung tissue of the Valsartan group were significantly higher than that of BLM group (0.23 ±0. 02 vs0. 36 ±0.03, P ＜0.01). Conclusions Valsartan could alleviate acute lung injury in rats, which probably be due to the expression decrease of TGF-β1 and Smad2/3 and the expression increase of Smad7 in lung tissues.