过氧化物酶体增殖物活化受体γ激动剂罗格列酮对慢支大鼠肺组织基质金属蛋白酶-9表达的影响

Effect of PPARγ Activators Rosiglitazone on Matrix Metalloproteinase-9 in Rats COPD

目的研究过氧化物酶体增殖物活化受体γ(PPARγ)的外源性强力配体激动剂罗格列酮(RGD)对慢支大鼠肺组织基质金属蛋白酶-9(MMP-9)表达的影响。方法采用熏烟加气管内滴注内毒素法建立慢性阻塞性肺疾病(COPD)大鼠模型,用酶联免疫吸附实验、实时定量PCR等方法分别测定其MMP-9基因及蛋白水平表达的改变。同时为了进一步探讨罗格列酮在肺部微环境下对基质金属蛋白酶9活性的影响,通过支气管肺泡灌洗法得到了正常及慢支大鼠的肺泡巨噬细胞,使之与罗格列酮共同培养,观察其对肺泡巨噬细胞MMP-9表达的影响。结果用熏烟加气管内滴内毒素法建立的大鼠COPD模型,其病理形态学改变与人类COPD的改变相似。罗格列酮可以抑制烟雾和内毒素刺激所致大鼠肺组织MMP-9 mRNA及蛋白表达的增加。结论罗格列酮对COPD的防治作用可能是由于抑制了MMP-9mRNA表达进而抑制了MMP-9蛋白表达所致。

Objective To study the effect of strongly exogenous agonist rosiglitazone（RGD） of peroxisome proliferator-activated receptor γ（PPARγ） on matrix metalloproteinase-9（MMP-9） expression of lung tissue from chronic obstructive pulmonary disease（COPD） rats.Methods COPD rat model was established by fumigation cigarettes plus intratracheal instillation of endotoxin.MMP-9 gene and protein expression changes were measured by real-time quantitative PCR and enzyme-linked immunosorbent assay.Meanwhile,in order to further explore the effect of rosiglitazone on matrix metalloproteinase-9 activity under the lung microenvironment,normal and chronic bronchitis alveolar macrophages obtained by bronchoalveolar lavage were cocultured with rosiglitazone and its effect on MMP-9 expression of alveolar macrophages was observed.Results The pathological changes of bronchi and lung tissue from rat COPD model established by fumigation cigarettes plus endotoxin endotracheal drop were similar to those of human COPD.Rosiglitazone can inhibit increased MMP-9 mRNA and protein expression from smoke and LPS-induced rat lung tissues.Conclusion The prevention and treatment effect of rosiglitazone on COPD may be due to inhibition of MMP-9 mRNA thereby inhibiting the expression of MMP-9 protein.