新型内皮素受体拮抗剂ETP-508对实验性大鼠肺纤维化的干预作用

目的：研究新型内皮素受体拮抗剂ETP-508对实验性大鼠肺纤维化的干预作用，并探讨其机制．方法：实验分为4组：博莱霉素组、ETP-508组、地塞米松组和正常对照组．博莱霉素组、ETP-508组和地塞米松组均给以博莱霉素（5mg／kg）气管内注射复制大鼠肺纤维化模型，正常对照组给以气管内注射等量生理盐水替代．ETP-508组和地塞米松组造模开始后次日又分别给以腹腔注射ETP-508（100μg／kg）和地塞米松（1mg／kg），隔日1次．博莱霉素组和正常对照组以等量生理盐水替代．造模后第28日处死所有大鼠，测定肺组织ET-1和羟脯氨酸含量，并进行组织病理学观察．结果：博莱霉素组肺组织内羟脯氨酸明显高于正常对照组，病理为肺纤维化改变．博莱霉素组的ET-1水平高于正常对照组和地塞米松组，差异有统计学意义（P〈0．01）；ETP-508组ET-1水平均高于上述各组，与博莱霉素组（P〈0．05），正常对照组和地塞米松组比较（P〈0．01）有统计学意义；地塞米松组与正常对照组比较，无统计学意义（P〉0．05）．结论：ETP-508对肺纤维化的形成有一定的干预作用，其机制可能通过拮抗ET-1与内皮素受体结合的作用有关．

Effects of ETP-508,a novel endothelin receptor antagonist,on bleomycin-induced pulmonary fibrosis in rats

AIM： To investigate the effects of ETP-508, a novel endothelin receptor antagonist, on bleomycin （ BLM ） -induced pulmonary fibrosis in rats. METHODS ： Rats were divided into 4 groups： BLM group, ETP-508 group, dexamethasone group and control group. Pulmonary fibrosis was induced by endotracheal injection of bleomycin （5 mg/kg）. ETPS08 group was treated with intraperitoneal injection of ETP-508 （100 μg /kg, every other day）, dexamethasone group was treated with intraperitoneal injection of dexamethasone （1 mg/kg, every other day） and BLM model group and control group were treated with saline. At the 28th day, the rats were executed and the concentrations of ET-1 and hydroxyproline （HYP） in lung tissues were determined. Histopathological examination was conducted. RESULTS： HYP concentrations in BLM group were significantly higher than those of the other groups and histopathological examination showed fibrosis. ET-1 concentrations of BLM group were significantly higher than those of control group and dexamethasone group （P 〈 0.01 ）. ET-1 concentrations in ETP508 group were higher than those of other groups, with significant differences from those in control group and dexamethasone group （ P 〈 0.01, respectively） and BLM group （P 〈 0.05 ）. There were no significant differences between control group and dexamethasone group （P 〉 0. 05 ）. CONCLUSION： ETP-508, a novel endothelin receptor antagonist, has restraining effects on the pulmonary fibrosis formation, which may result from the prevention of the banding of ET-1 and endothelin receptor.