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作者：王光辉，金发光，楚东岭，段丽
【关键词】  哮喘；气道重构；明胶酶B；金属蛋白酶1组织抑制剂
    【Abstract】 AIM:  To investigate  the roles  of matrix metalloproteinase9  (MMP9)  and tissue inhibitor of metalloproteinase1 (TIMP1) in airway remodeling of asthmaric guinea  pigs. METHODS:  Guinea pigs  were sensitized with ovalbumin conjuncted with Al(OH)3， and subsequently challenged repeatedly with  ovalbumin  aerosol. The guinea  pigs  were  randomly divided into the control group，asthmatic 4, 6, 8week groups. The expressions of MMP9  and  TIMP1  in bronchi and lung tissues were observed by immunohistochemistry  combined with the microimage analysis．The levels of MMP9 mRNA  and TIMP1 mRNA  were determined by  semiquantitative PCR. RESULTS:  ① After  repeated allergen challenge, smooth  muscle  hyperplasia  was obvious  in guinea pig bronchi．Expression levels of MMP9  and  TIMP1 in the epithelial cells of bronchi were significantly higher in asthmatic animals  than those of control group． ② The expression of MMP9  in asthmatic guinea pigs  lung tissues was  0.52±0.05 in 4week  group, 0.74±0.05 in 6week group, 0.48±0.04 in 8week group , 0.21±0.04 in control group  （P<0.05）. The expression of  TIMP1 in asthmatic guinea  pigs lung tissues was 0.36±0.04  in 4week group,0.83±0.05 in  6week  group, 0.97±0.05  in  8week  group , 0.20±0.02  in control group  （P<0.05）. ③ The results of immunocytochemistry  were consistent with those of RTPCR. ④ The upregulation of MMP9 expression become  slower than TIMP1 since the 4th week in  asthmatic animals. So ratio of MMP9/ TIMP1  was decreased. CONCLUSION:  The expression levels of MMP9  and  TIMP1 were closely correlated  with asthma airway remodeling, and the ratio of MMP9/ TIMP1  may reflecte the degree of asthma airway remodeling.
    【Keywords】 asthma;  airway remodeling; gelatinase B;  tissue inhibitor of  metalloproteinase1
    【摘要】 目的： 探讨哮喘豚鼠模型中基质金属蛋白酶（MMPs）及其组织抑制因子(TIMP)在哮喘气道重构发病中的作用. 方法： 重复雾化吸人卵蛋白建立豚鼠哮喘气道重构模型. 实验分为对照组、哮喘激发4, 6 和8 wk组. 免疫组化方法结合显微图像分析检测MMP9, TIMP1的表达. 半定量PCR检测MMP9及TIMP1mRNA水平. 结果：  ① 哮喘各组动物均出现管壁增厚、平滑肌增生等气道重构的特征性改变. ② 哮喘豚鼠MMP9的mRNA表达：哮喘4 wk组为（0.52±0.05），哮喘6 wk组为（0.74±0.05）；哮喘8 wk组为（0.48±0.04）；对照组

为（0.21±0.04）；哮喘各组与对照组组间比较差异有统计学意义（P<0.05). 哮喘豚鼠TIMP1的mRNA水平： 哮喘4 wk组为（0.36±0.04）；哮喘6 wk组为（0.83±0.05）；哮喘8 wk组为（0.97±0.05）；对照组为（0.20±0.02）；哮喘各组与对照组组间比较差异有统计学意义（P<0.05）. ③ 免疫组化的结果和RTPCR的结果一致. ④ 在哮喘各时段组中，MMP9的表达增高自第4 wk时明显变缓，而TIMP1仍持续增高，导致MMP9/ TIMP1比例下降. 结论： 哮喘的气道重构与MMP9 和TIMP1的表达密切相关，而二者的比例可能反映气道重构的严重程度.
    【关键词】 哮喘；气道重构；明胶酶B；金属蛋白酶1组织抑制剂
    气道重构是气道反复炎症损伤与修复的结果，是造成哮喘患者不可逆气道阻塞的病理生理基础，主要表现为细胞外基质（extracellular  matrix,  ECM）的沉积、基底膜增厚、气道平滑肌增生和肥厚等改变. 其中ECM在气道壁沉积过多是引起气道壁纤维化和气流阻塞的主要原因之一［1］. 正常ECM的合成与降解处于一个动态平衡之中，基质金属蛋白酶9(matrix metalloproteinases, MMP9)与基质金属蛋白酶抑制因子1（tissue inhibitor of metalloproteinase, TIMP1）平衡是维持ECM内环境稳定的决定因素［2］. 本实验通过复

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