香烟暴露对大鼠肺组织及人血管内皮细胞MMP-9和TIMP-1表达的影响

Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Rat Lung Tissue and Human Vascular Endothelial Cells after Cigarette Smoke Exposure

目的探讨香烟暴露对大鼠肺组织及人血管内皮细胞基质金属蛋白酶9(MMP-9)和金属蛋白酶组织抑制因子1(TIMP-1)表达的影响。方法采用烟熏法建立慢性阻塞性肺疾病(COPD)模型,记录模型组(M组)及对照组(N组)大鼠的一般观察指标、肺功能指标、肺组织病理学指标、支气管肺泡灌洗液(BALF)中白细胞计数和分类及肺组织中MMP-9和TIMP-1的表达。用Western blot检测不同浓度香烟提取物干预后人血管内皮细胞中MMP-9和TIMP-1表达的变化趋势。结果M组大鼠出现毛发脱落、反应迟钝、呼吸频率加快等变化。M组与N组比较,大鼠BALF中炎性细胞计数、肺组织形态学指标、肺功能指标、肺组织MMP-9和TIMP-1的表达及MMP-9/TIMP-1的差异均有统计学意义(P<0.05)。随着香烟提取物浓度增高,人血管内皮细胞中MMP-9和TIMP-1的表达逐渐增强。结论吸烟是COPD的一个重要致病因素。肺内MMP-9/TIMP-1的失衡及血管内皮细胞中MMP-9和TIMP-1的表达可能在COPD的发生发展中起一定作用。

Objective To study the expressions of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP- 1 ） in rat lung tissue and human vascular endothelial cells after cigarette smoke exposure. Methods The rat model of chronic obstructive puhnonary disease （COPD） was established by exposure to cigarette smoke. The general condition, lung function, pathological features,white blood cell count and classification in the bronchoalveolar lavage fluid （BALF）,and expressions of MMP-9 and TIMP-1 in the lung tissue were determined in COPD group （group M） and control group （group N）. Western blot was performed to detect the expressions of MMP-9 and TIMP-1 in the vascular endothelial cells exposed to different concentrations of cigarette smoke extract. Results The changes such as hair falling, dullness and rapid breathing appeared in the rats of group M. There were significant differences in the histomorphologic characteristics of the lung tissue, lung function, count of inflammatory cells in BALF, expressions of MMP-9 and TIPM- 1, and ratio of MMP-9/TIMP- 1 between groups N and M. The expressions of MMP-9 and TIMP-1 in the vascular endothelial cells increased with the concentration of cigarette smoke extract. Conclusion Smoking is one of the key pathogenic factors for COPD. The imbalance of MMP-9/TIMP-1 in the lung tissue and the expressions of MMP-9 and TIMP-1 in the vascular endothelial cells may play an important role in the pathogenesis of COPD.