糜酶抑制剂对大鼠肺纤维化干预作用及对血管紧张肽Ⅱ及其受体.doc

糜酶抑制剂对大鼠肺纤维化干预作用及对血管紧张肽Ⅱ及其受体 　 作者：顾燕兰, 郑金旭, 万兵, 管淑红 【摘要】 目的： 观察糜酶抑制剂（ChyI）对博莱霉素（BLM）致大鼠肺纤维化模型的干预作用和对血管紧张肽Ⅱ及其受体的影响，探讨糜酶参与肺纤维化的机制。方法： 健康SD大鼠60只随机分3组：正常对照组（生理盐水），模型组（博莱霉素），干预组（博莱霉素＋糜酶抑制剂）。分别在第7，14，21，28天，每组HE染色5只大鼠，观察支气管肺组织病理改变，免疫组化观察肺组织中血管紧张肽Ⅱ及其受体的表达。结果： （1）肺泡炎程度评价：干预组和模型组与对照组间比较，差异有统计学意义，但干预组和模型组间差异无统计学意义。（2）肺纤维化程度评价：干预组和模型组与对照组间差异有统计学意义，且干预组和模型组之间比较，差异亦有统计学意义。（3）血管紧张肽Ⅱ及其受体的表达分析：模型组肺间质中血管紧张肽Ⅱ及其受体表达均持续增强,干预组均明显减少。结论： 糜酶抑制剂能减轻博莱霉素诱导的大鼠肺纤维化，可能是通过下调血管紧张肽Ⅱ及其1型受体(AT1)的表达而起作用。 【关键词】 肺纤维化； 糜酶； 血管紧张肽Ⅱ 　　［Abstract］ Objective: To study the effect of chymase inhibitor on bleomycininduced pulmonary fibrosis in rats and its possible mechanism. Methods： Sixty female rats were randomly divided into three groups: the model group, the control group and the chymase inhibitor treatment group, in which the rats were intratracheally instilled with(5mg/kg) bleomycin. From the first day after bleomycin challenge, by every day, the chymase inhibitor treatment group was perfused intostomach daily chymase inhibitor(10 mg/kg), the other group were given sterile saline. Five rats were killed each group respectively at the time of the seventh day, the fourteenth day, the twentyfirst day and the twentyeighth day. The pathological changes of lung tissue by hematoxylineosin staining were investigated. The expression of angiotensinⅡ， AT1 receptor in bronchial lung tisusue were examined by immunohistochemical analysis. Results： Alveolitis in the model group and the ChyI group were significantly lower as compared with the control, but there were no significant difference between the model group and ChyI group. Level of pulmonary fibrosis was inhibited evidently after the treatment by chymase inhibitor. The expression of angiotensin Ⅱ， AT1receptor，in the lung fibrosis of BLM group was higher than in control group with significant difference, and treatment group was lower than BLM group with significant difference. Conclusion： Chymase inhibitor can alleviate BLM induced pulmonary fibro