摘要
目的 :观察博来霉素致肺纤维化大鼠模型肺组织基质金属蛋白酶 2 (matrixmetalloproteinase 2 ,MMP 2 )、基质金属蛋白酶 9(matrixmetalloproteinase 9,MMP 9)、膜型基质金属蛋白酶 1(membranetypemetrixmetallopro teinase 1,MT1 MMP)及组织型金属蛋白酶抑制物 (tissueinhibitorofmetalloproteinase,TIMP) 1、TIMP 2的表达 ,探讨其在肺损伤与修复过程的作用 ,进一步阐明肺间质纤维化的发病机制。方法 :采用博来霉素致Wistar大鼠肺纤维化模型 ,RT PCR法半定量测定大鼠肺组织MMP 2、MMP 9、MT1 MMP及TIMP 1mRNA的表达 ;免疫组化方法观察MMP 2、MMP 9、TIMP 1及TIMP 2在大鼠肺组织的表达。结果 :MMP 2、MMP 9、MT1 MMP及TIMP 1mRNA在正常肺组织中均有少量表达 ,分别为 0 .0 72± 0 .0 2 3,0 .334± 0 .0 89,0 .0 38± 0 .0 13及 0 .0 98± 0 .0 30 ;给予博来霉素后 1周 ,MMP 2、MT1 MMP及TIMP 1mRNA表达显著增加 ,分别为 0 .4 35± 0 .0 5 8,0 .312± 0 .0 78和0 .5 2 6± 0 .12 0 (与对照组相比 ,P <0 .0 5 ) ;至第 4周时上述 3种mRNA表达明显下降 ,但仍比正常对照组显著增高(0 .12 6± 0 .0 5 0 ,0 .0 6 4± 0 .0 2 2及 0 .179± 0 .0 31,与对照组及 1周组相比 ,P <0 .0 5 ) ;MMP
Objective: To observe the expression of matrix metalloproteinase 2 (MMP 2), MMP 9, membrane type matrix metalloproteinase 1 (MT1 MMP) and their tissue inhibitor of metalloproteinase 1 (TIMP 1) and TIMP 2 in the rat model of bleomycin induced pulmonary fibrosis, and find out the roles that matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play in the development of pulmonary fibrosis.Methods: Wistar rats were intratracheally administrated bleomycin A5 (5 mg·kg 1 ). The mRNA of MMP 2, MMP 9, MT1 MMP and TIMP 1 in the lung homogenate were measured by semi quantitative rt PCR. The expressions of MMP 2, MMP 9, TIMP 1 and TIMP 2 in lungs were observed by immunohistochemestry. Results: A small quantity of MMP 2, MMP 9, MT1 MMP and TIMP 1 mRNA were measured in normal lungs (0.072±0.023,0.334± 0.089, 0.038±0.013 and 0.098±0.030, respectively), and the expression increased significantly on the 7 th day after bleomycin administration (0.435±0.058,0.312±0.078 and 0.526±0.120, respectively, P <0.05). On the 28th day, the expression of MMP 2, MT1 MMP and TIMP 1 reduced but still remained significantly higher than normal (0.126±0.050,0.064±0.022 and 0.179± 0.031, respectively, P <0.05), and the expression of MMP 9 continued at a high level (0.639± 0.153). Normal lung tissues showed weak positive reaction with MMP 2,MMP 9,TIMP 1 and TIMP 2 in immunohistochemistry,and the staining of MMP 2,MMP 9,TIMP 1 and TIMP 2 increased significantly on the 7th day.On the 28th day,the expression of MMP 2,MMP 9 and TIMP 1 reduced but were still significantly higher than normal,and that of TIMP 2 continued at a high level.Conclusion:These findins suggest that (1) MMP 2 and MMP 9 may play important roles in the alveolar injury and alveolar inflammation by degradating the epithelial basement membrane, and MMP 9 may be involved in the development of pulmonary fibrosis. (2) The activity of MMP 2 was increased not only by the up regulation at transcriptional level but also by the reinforcement of the activation of its proenzyme, and MT1 MMP plays a role through the activation of MMP 2 in the process of pulmonary fibrosis. (3) TIMP 1 and TIMP 2 may participate in the development of pulmonary fibrosis by inhibiting the degradation of extracellular matrix and may be involved in alveolar inflammation and alveolar repair
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2002年第6期716-721,共6页
Journal of Peking University:Health Sciences
基金
北京自然科学基金 (70 12 0 2 2 )~~
