反复细菌感染致大鼠气道重构中结缔组织生长因子的表达变化及意义

Role of connective tissue growth factor in airway remodeled in rats induced by repeated bacterial infection

目的:探讨反复铜绿假单胞菌(Pseudomonas aeruginosa,PA)感染致大鼠气道重构中结缔组织生长因子(connective tissue growth factor,CTGF)的表达变化及意义。方法:通过多次经气管穿刺注入一定剂量PA菌液,建立大鼠慢性肺部感染模型。观察气管及肺组织的病理改变,测定气管壁和血管壁厚度。通过免疫组化检测肺组织CTGF蛋白的表达,同时采用real-time RT-PCR方法检测肺组织CTGF mRNA的表达变化,分析CTGF表达与病理改变的相关性。结果:大鼠感染PA第4周开始,气管壁厚度和血管壁厚度均较NS组显著增加(P<0.05),至第16周,各级支气管管壁增厚,管腔明显狭窄,有气道重构和肺气肿形成。免疫组化以及real-time RTPCR结果显示CTGF表达随着时间的延长逐渐增强,与对照组相比差异有统计学意义(P<0.01),与气管壁和血管壁厚度呈显著正相关(r=0.880,r=0.829,P<0.01)。结论:气道反复感染铜绿假单胞菌可致大鼠出现气道重构,而CTGF可能参与了气道重构的发生和发展过程。

AIM：To investigate the role of connective tissue growth factor（CTGF） in airway remodeling in rats induced by repeating Pseudomonas aeruginosa（PA） infection.METHODS：The rats were intratracheally injected with PA for 12 times to induce chronic lung inflammation.The pathological changes of the trachea and lungs were observed,and the thickness of the trachea wall and vessel wall was measured.At the same time,the methods of immunochemistry and real-time quantitative RT-PCR were used to determine the protein and mRNA expression of CTGF in the lung tissues.The relevance between pathological changes and CTGF expression was also analyzed.RESULTS：From the 4th week,the thickness of the trachea wall and vessel wall in infectious group was larger than that in NS group（P〈0.05）.At the 16th week,obvious chronic inflammation in all grade bronchi appeared,the trachea walls were thickened and the lumens were narrowed in the infected animals.The expression of CTGF was significantly up-regulated（P 0.01） with positive correlations to the thickness of the trachea wall and vessel wall（r=0.880,r=0.829,P〈0.01）.CONCLUSION：Airway remodeling in rats is induced by repeated injection of PA.CTGF may play some roles in the pathogenesis of airway remodeling.