缬沙坦对博莱霉素所致大鼠肺纤维化的干预研究

目的观察AT1受体拮抗剂缬沙坦对博莱霉素A5（BLMA5）所致大鼠肺纤维化模型形成过程的影响。方法54只SD雄性大鼠随机分为正常对照组（C组）、模型对照组（B组）和缬沙坦治疗组（T组）3组，18只／组。T组于大鼠气管内滴注0．5％BLMA5生理盐水溶液（5mg／kg）以复制肺纤维化动物模型，并于造模当天每日给予缬沙坦（20mg／kg）灌胃；B组以生理盐水代替缬沙坦灌胃；C组则均用生理盐水代替BLMA5和缬沙坦。各组动物均于制模开始后的第7、第14、第28天分别随机处死6只动物，分取肺组织行病理切片HE染色和Masson染色于光镜下观察大鼠早期肺泡炎程度以及晚期肺纤维化程度、碱水解法检测肺组织羟脯氨酸（Hyp）浓度、免疫组化技术检测肺组织平滑肌肌动蛋白（α—SMA）和转化生长因子TGF—β1水平。结果（1）肺组织Hyp含量：制模第7天3组动物间比较差异均无统计学意义（P〉0．05）；第14天和第28天，B组肺组织Hyp含量较C组明显升高（P〈0．01），T组较B组Hyp含量明显下降（P〈0．01）。（2）早期肺泡炎程度：HE染色可见B组在第7天时急性肺损伤、肺泡炎程度最为明显，可见肺泡间隔和肺泡腔内有大量炎性细胞浸润，肺泡隔增宽，其后炎症渐有减轻，但第14天和第28天时炎症仍较C组明显（P〈0．01）；T组在第7、第14天和第28天肺泡炎程度均较B组明显减轻（P〈0．05）。（3）晚期肺纤维化程度：Masson染色在第7天3组动物间肺纤维化程度差异无统计学意义，第14、第28天时B组可见胸膜下、大气道及血管壁周围的基质胶原明显及纤维组织增多，较C组差异有统计学意义（P〈0．01），T组较B组肺纤维化程度明显减轻（P〈0.05）。（4）肺组织TGF—β1蛋白表达水平：B组第7天时肺组织内TGF-β1表达水平最强，以后逐渐减低，但与C组比较仍显著升高（P〈0．01）；T组TGF—

The study of valsartan on pulmonary fibrosis in rats Induced by bleomycin

Objectives To study the effect of valsartan, angiotensin type I receptors antagonist, on rat model of pulmonary fibrosis induced by bleemycin （BLM）. Methods Fifty-four adult male Sprague-Dawley rats were equally divided into three groups in random： Bleomycin group （M group）, control group （C group） and valsartan group （T group）. T group was treated with valsartan everyday at a dose of 20mg/kg after a single intratracheal instillation of bleomycin at a dose of 5mg/kg. M group was treated with saline instead of valsartan after an instillation of bleomycin. T group was treated with saline instead of valsartan and bleomycin. At the 7th, lgth and 28th day after instillation, six rats in each group were killed. The lung tissues were harvested for HE and Masson ＇s trichrome stain, the concentration of hydroxyproline in the lung was determined and the immunohistochemistry was used to detect the expressions of α-SMA and TGF-β1 in the rat lung tissues. Results The hydroxyproline content of M group was significantly higher than that of T group. The degrees of alveolitis in T group were ameliorated, compared with those in M group. Pulmonary fibrosis in T group was significantly alleviated, compared with those in M group. The expressions of TGF-β1 and α-SMA in lung tissue of T group were significantly less than that of M group. Conclusions Valsartan could relieve the pulmonary fibrosis induced by bleomycin in rats. Valsartan may inhibit the proliferation of fibroblasts by suppressing the expression of TGF-β1 in lung tissue.