波生坦对肺间质纤维化的治疗作用  

Effects of bosentan on pulmonary fibrosis

作　　者：左万里[1] 赵洁敏[1] 黄积雄[1] 周伟[2] 黄炎明[1] 黄艳芬[1] 

机构地区：[1]中山大学附属江门医院江门市中心医院呼吸内科,广东江门529000 [2]中山大学附属江门医院江门市中心医院病理科,广东江门529000

出　　处：《中华实验外科杂志》2014年第3期591-593,F0004,共4页Chinese Journal of Experimental Surgery

摘　　要：目的 观察波生坦对肺纤维化（PF）的疗效.方法 48只雄性Wistar大鼠随机均分为6组：对照2、4周组（C2、C4）、模型2、4周组（F2、F4）和治疗组（D1、D2）;予以博来霉素建模;DI、D2组分别于2、15d予以波生坦灌胃.2、4周末测定各组大鼠血浆内皮素-1（ET-1）、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶抑制剂-1（TIMP-1）水平,光镜下观察肺组织肺泡炎、纤维化的程度.结果 （1）造模后ET-1随时间延长升高[（0.10±0.05）、（0.11 ±0.04）、（0.28±0.08）、（0.41±0.13）μg/L],D1组较F4组下降,D2组与F4组差异无统计学意义（P＞0.05）.（2）病理形态观察：模型组肺泡架构破坏,早期炎性细胞聚集,后期成纤维细胞、胶原纤维增生;早期波生坦治疗病变减轻.（3）ET-1与肺泡炎、纤维化评分呈正相关,MMP-9/TIMP-1与肺泡炎、纤维化评分呈负相关.结论 波生坦可延缓PF进展,早期治疗对肺泡炎、纤维化改善更明显.Objective To investigate the effects of bosentan on pulmonary fibrosis.Methods Forty-eight male Wistar rats were randomly and equally divided into control groups （C2,C4）,model groups （F2,F4） and drug groups （D1,D2）.Bleomycin was used to create pulmonary fibrosis model,while rats in D1 and D2 groups were treated by bosentan from day 2 and day 15.Plasma endothelin-I （ET-1）,matrix metalloproteinase-9 （MMP-9） and tissue inhibitorof metalloproteinase （TIMP）-1 were measured.Alveolitis and fibrosis scores were assessed after 2 and 4 weeks.Results （1） The levels of ET-1 in F4 group were highest,followed by F2,C4 and C2 groups [（0.41 ±0.13）,（0.28 ±0.08）,（0.11 ±0.04）,and （0.10 ±0.05） μg/L].Compared to F4 group,the levels of ET-1 in D1 group was reduced,but no significant difference was found between D2 and F4 groups; （2） Pathological assessment showed that alveolar structure was destroyed,and numerous inflammatory cells and fibroblasts could be seen in F2 group as well as collagen,most significantly in F4 group,and those were significantly reduced in D1 group as compared with F4 ; （3） The levels of ET-1 were positively associated with alveolitis and fibrosis scores,but MMP-9/TIMP-1 were negatively with them.Conclusion Bosentan can protect against the bleomycin-induced pulmonary fibrosis,and the improvement is more significant in early stage.

关 键 词：波生坦 博来霉素 肺间质纤维化 内皮素-1 

分 类 号：R563[医药卫生—呼吸系统]