摘要
目的:本实验采用两种小鼠急性肺损伤与肺纤维化相关的模型,探讨新内皮素受体拮抗剂CPU0213对肺纤维化病变明显的肺动脉高压是否具有改善作用。方法:实验分正常组、博莱霉素或油酸模型组、阳性药硝苯地平(10mg/kg)组和CPU0213(50、100、200mg/kg)治疗组(n=10)。博莱霉素模型中,观察肺重系数、支气管肺泡灌洗液(BALF)回收率、BALF白细胞数量及分类、丙二醛(MDA)含量以及肺组织羟脯氨酸含量。油酸模型中,小鼠尾静脉注射伊文氏兰(50mg/kg)1h后,接着静注油酸100mg/kg,4h后分离左肺,烘干后测定小鼠左肺中伊文氏兰的含量。结果:CPU021350、100、200mg/kg可以降低肺重系数,减少肺组织和血清MDA含量,减少肺组织羟脯氨酸含量,降低油酸所致肺纤维化模型中肺组织通透性的增加。其中,CPU0213200mg/kg的治疗效果优于阳性药硝苯地平(10mg/kg)。结论:内皮素受体拮抗剂CPU0213能减轻小鼠两种急性肺损伤与纤维化病变,对临床肺动脉高压有较好疗效。
AIM：Pulmonary fibrosis（PF） is closely related to progression of pulmonary artery hypertension.The study is aimed to investigate the effects of endothelin receptor antagonist CPU0213 on PF induced by bleomycin or oleic acid in mice.METHODS：Mice were divided into control,PF model,nifedipine treated（p.o.10 mg·kg^-1·d^-1）,and CPU0213（p.o.50 mg·kg^-1·d^-1）,CPU0213（p.o.100 mg·kg^-1·d^-1）,CPU0213（p.o.200 mg·kg^-1·d^-1） treated groups（n=10）.In bleomycin-induced PF model,the lung weight index,recovery of bronchioalveolar lavage fluid（BALF）,leukocytes in BALF and biochemical assay of malondialdehyde（MDA） and hydroxyproline were delected.In oleic acid-induced acute lung injury model,mice received intravenous injection of Evan＇s blue,and 4hr later the content of Evan＇s blue in lung were measured.RESULTS：CPU0213 and nifedipine were effective in decreasing lung weight,suppressing inflammatory reactions,oxidative stress,and the accumulation of hydroxyproline in bleomycin-induced PF model.In acute lung injury model,the content of Evan＇s blue in lung was reduced by CPU0213 and nifedipine.The improvement made by CPU0213 200 mg/kg was better than nifedipine 10 mg/kg.CONCLUSION：Endothelin receptor antagonist CPU0213 showed favorable ability to reverse changes developed in PF.CPU0213 may be promising in the treatment of pulmonary artery hypertension in clinical settings.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2007年第9期998-1003,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金面上课题(30670760)资助项目
关键词
博莱霉素
内皮素受体拮抗剂
油酸
肺纤维化
肺动脉高压
bleomycin
endothelin receptor antagonists
oleic acid
pulmonary fibrosis
pulmonary artery hypertension
