缬沙坦对肺纤维化模型的干预作用及其对肝细胞生长因子表达的影响  

Effects of valsartan on bleomycin-induced pulmonary fibrosis in rats and the expression of hepatocyte growth factor in lung tissue

作　　者：刘芳[1] 徐启勇[1] 叶燕青[1] 

机构地区：[1]武汉大学中南医院呼吸科,430071

出　　处：《中华结核和呼吸杂志》2005年第7期479-483,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的研究血管紧张素Ⅱ受体拮抗剂缬沙坦对肺纤维化模型的干预作用及其可能的机制。方法60只Wistar大鼠采用随机数字表法随机分成3组,每组20只:(1)缬沙坦组,经气管插管灌注博莱霉素(BLM)诱导肺纤维化,随后每日用缬沙坦16mg/kg灌胃进行干预;(2)模型组,气管内灌注用BLM,灌胃用生理盐水;(3)对照组,气管内灌注和灌胃均用生理盐水。各组动物于气管内灌注后第7、14、28、42天分别处死5只。取肺组织经苏木精-伊红、Masson胶原染色及测定羟脯氨酸浓度来评价治疗效果。用免疫组化及原位杂交方法分别检测转化生长因子β(TGF-β)蛋白和肝细胞生长因子(HGF)mRNA在肺内的表达。用酶联免疫吸附测定(ELISA)法检测HGF蛋白在大鼠肺组织的含量。结果缬沙坦组肺泡炎程度在第14、28、42天分别为(0·88±0·12)、(0·79±0·21)、(0·75±0·17)分,低于同期模型组的(2·05±0·25)、(1·38±0·12)、(1·19±0·11)分,差异均有统计学意义(P均<0·01);缬沙坦组肺纤维化程度在第7、28、42天分别为(0·28±0·03)、(1·74±0·18)、(1·91±0·09)分,也低于同期模型组的(0·45±0·10)、(2·08±0·32)、(2·77±0·15)分,差异均有统计学意义(P均<0·05);缬沙坦组肺组织羟脯氨酸含量在第14、42天分别为(1·08±0·13)、(1·39±0·20)μg/mg·pro,低于同期模型组的(1·45±0·19)、(2·19±0·37)μg/mg·pro,差异均有统计学意义(P均<0·01);缬沙坦组肺组织中TGF-β蛋白表达在早、晚期分别为2·27±0·30、2·05±0·18,均低于同期模型组的3·99±0·43、2·71±0·46,差异均有统计学意义(P均<0·05)。缬沙坦组HGFmRNA表达在早、晚期分别为1·61±0·20、0·52±0·19,均高于同期模型组的1·98±0·23、0·28±0·14,差异均有统计学意义(P均<0·05);缬沙坦组蛋白含量在早、晚期分别为(203±18)、(129±20)pg/ml,均高于同期模型组的(260±21)、(100±20)pg/ml,差异均有统计学意义(P均<0·05)。结论缬沙坦�Objective To study the effect of valsartan on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods Sixty Wistar rats were divided into three groups. In the valsartan group and the model groups, pulmonary fibrosis was induced by intratracheal instillation of bleomycin(BLM), and then the former group reveived valsartan 16 mg/kg daily, but the latter group received oral normal saline. In the control group, normal saline was given both intratracheally and orally. Five rats in each group were sacrificed 7,14,28,and 42 days after intratrachel instillation. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Histological changes of the lungs were evaluated by HE stain and Masson′s trichrome stain. Lung expression of transforming growth factor-β (TGF-β) protein was assessed by immunohistochemistry. The mRNA of hepatocyte growth factor (HGF) was detected by in situ hybridization, and the level of HGF protein was further measured by ELISA. Results In the valsartan group, alveolitis [(0.88±0.12)points,(0.79±0.21)points, (0.75±0.17)points] decreased significantly 14 days after treatment with BLM and was significantly lower as compared with the model group[(2.05±0.25)points, (1.38±0.12)points, (1.19±0.11)points, P<0.01]. Pulmonary fibrosis on day 7,28,42[(0.28±0.03)points vs(0.45±0.10)points, (1.74±0.18)points vs( 2.08±0.32)points, (1.91±0.09)points vs(2.77±0.15)points, P<0.05], hydroxyproline concentrations on day 14,42[(1.08±0.13)μg/mg·pro vs(1.45±0.19)μg/mg·pro,(1.39±0.20)μg/mg·pro vs(2.19±0.37)μg/mg·pro, P<0.01] and protein expession of TGF-β on day 7,42[2.27±0.30 vs 3.99±0.43, 2.05±0.18 vs 2.71±0.46, P<0.05] in the valsartan group all reduced significantly as compared with that of the model group. HGF mRNA [1.61±0.20 vs 1.98±0.23,0.52±0.19 vs 0.28±0.14,P<0.05] and its protein expression(204±18)pg/ml vs (260±21) pg/ml,(129±20)pg/ml vs (100±20)pg/ml,P<0.05) on day 7 and day 42 in the valsartan group were increased as compared

关 键 词：肝细胞生长因子 肺纤维化模型 缬沙坦 干预作用 酶联免疫吸附测定(ELISA) 血管紧张素Ⅱ受体拮抗剂 转化生长因子β(TGF Wistar大鼠 TGF-β MASSON 原位杂交方法 mRNA表达 生理盐水 统计学 大鼠肺组织 纤维化程度 气管内 

分 类 号：R563.9[医药卫生—呼吸系统]