氯沙坦对大鼠肺纤维化模型的干预作用及对MCP-1和bFGF表达的影响  

Losartan in the rat model of bleomycin-induced pulmonary fibrosis and its impact on the expression of monocyte chemoattractant protein-1 and basic fibroblast growth factor

作　　者：方向群[1] 朱元珏[1] 胡晓玲 留永健[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院呼吸科,北京100730

出　　处：《中华结核和呼吸杂志》2002年第5期268-272,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的　研究血管紧张素Ⅱ的 1型受体拮抗剂氯沙坦对大鼠肺纤维化模型的干预作用及可能的机制。方法　Wistar大鼠经气管内灌注博莱霉素诱导肺纤维化 ,随后分别每日口服氯沙坦 1 0mg/kg(L组 )、泼尼松 (强的松 ) 2 0mg/kg(P组 )和生理盐水 (B组 )进行干预。对照组气管内和口服均用生理盐水。各组动物均于气管内灌药后第 3、7、1 4、2 8、56天分别处死 6只。通过苏木素 伊红染色、Masson胶原染色、天狼猩红染色偏光法及测定肺组织羟脯氨酸浓度来评价治疗效果。用逆转录聚合酶链反应 (RT PCR)检测单核细胞趋化因子 1 (MCP 1 )和碱性成纤维细胞生长因子 (bFGF)的mRNA在肺内的表达。用免疫组化及酶联免疫吸附测定 (ELISA)法检测MCP 1和bFGF蛋白在大鼠肺组织的表达。结果　L组的肺泡炎和肺纤维化程度及肺组织的羟脯氨酸含量显著地低于B组 ;其MCP 1和bFGF的蛋白表达显著地低于B组。结论　氯沙坦能减轻博莱霉素诱导的大鼠肺纤维化 ,这种作用有可能部分通过抑制MCPObjective To study the effect of losartan on bleomycin induced pulmonary fibrosis in rats and its possible mechanism.Methods Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin. Then the rats received daily losartan 10 mg/kg (group L), prednisone 20 mg/kg (group P), or normal saline (group B) orally . Normal controls received normal saline both intratracheally and orally. Six rats in each group were sacrificed 3,7,14,28 and 56 days after intratracheal instillation. Histological changes of the lungs were evaluated by HE stain, Masson′s trichrome stain and sirius red stain. Collagen content of the lung tissue was assessed by hydroxyproline concentration. The mRNAs of monocyte chemoattractant protein 1 (MCP 1) and basic fibroblast growth factor (bFGF) were detected by reverse transcription polymerase chain reaction(RT PCR). Lung expression of MCP 1 and bFGF proteins was assessed by immunohistochemistry and the level of MCP 1 protein was further measured by ELISA. Results Pulmonary fibrosis of group L and group P was improved as compared with that of group B. Hydroxyproline concentrations of group L and group P were lower than that of group B. Protein expression of MCP 1 and bFGF in group L was lower than that in group B.Conclusion Losartan alleviates bleomycin induced pulmonary fibrosis in rats. Inhibiting the expressions of MCP 1 and bFGF in lung tissues may be one of the mechanisms.

关 键 词：氯沙坦 肺纤维化 博莱霉素 单核细胞趋化因子 碱性成纤维细胞生长因子 治疗 

分 类 号：R563.905[医药卫生—呼吸系统]