结缔组织生长因子和周期蛋白D1在烟雾暴露大鼠肺血管重塑中的表达变化  

The expression variations of connective tissue growth factor and cycfinD1 in pulmonary vascular remodeling induced by cigarette smoke in rats

作　　者：王苒[1] 徐永健[1] 刘先胜[1] 曾大雄[1] 向敏[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院呼吸内科,武汉430030

出　　处：《中华结核和呼吸杂志》2010年第9期679-683,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金资助项目（30871128）

摘　　要：目的探讨烟雾暴露致大鼠肺血管重塑中结缔组织生长因子（CTGF）和周期蛋白D1的表达变化及其意义。方法健康雄性Wistar大鼠24只，按随机数字表法分为对照组，烟雾暴露2周、4周和8周组检测PaO2，HE染色和平滑肌细胞仪肌动蛋白染色观察肺血管重塑情况，行免疫组织化学染色观察CTGF和周期蛋白D1在肺动脉平滑肌中的表达，实时定量逆转录聚合酶链反应（qRT—PCR）检测肺动脉CTGF mRNA和周期蛋白D1 mRNA表达，Western blot法检测CTGF和周期蛋白D1的蛋白表达量。结果各组大鼠PaO2分别为（91±4），（92±5），（91±4），（93±4）mmHg（1mmHg：0．133kPa），差异均无统计学意义（F=0．15，P〉0．05）。随烟雾暴露时间的延长，肌化血管比例、肺血管壁厚度和血管直径比值（W／T）、CTGF和周期蛋白D1的mRNA和蛋白表达均呈时间依赖性增加，各组间比较差异均有统计学意义（F=51．06～590．20，P〈0．05）。CTGF与周期蛋白D1表达与肺W／T呈显著正相关（r=0．097～0．918，P〈0．01），二者的表达之间也呈显著正相关。结论烟雾暴露大鼠的CTGF和cyclin D1表达量均随暴露时间延长而显著升高，二者可能与烟雾暴露致肺动脉平滑肌细胞异常增殖有关。Objective To investigate the expression variations of connective tissue growth factor （CTGF） and cyclin D1 in pulmonary vasculature in rats exposed to cigarette smoke and their roles in pulmonary vascular remodeling. Methods Twenty-four male Wistar rats were randomly divided into 4 groups： 1 control group（C group）and 3 smoke exposure groups （S2w, S4w, S8w group）. Arterial partial pressure of oxygen was measured： Pulmonary artery remodeling was observed by Hematoxylin-Eosin staining and the percentage of muscularised small pulmonary arteries. Immunohistochemistry methods were performed to observe CTGF and cyclin D1 expressions in pulmonary artery smooth muscle. Real time quantitative RT- PCR and Western blot analysis were used for detection of mRNA and protein expressions in pulmonary artery smooth muscle. Results There was no significant difference in arterial partial pressure of oxygen among all groups. The percentage of muscularised small vessels and W/T were significantly increased in S2w, S4w and S8w group compared to control group（ P 〈 0.05 ）. Compared to control group, significant increases of CTGF and cyclinDl expressions in smoke exposure groups were observed （P 〈 0. 05 ）. The expressions of CTGF and cyclinD1 were significantly positively correlated with the severity of pulmonary vascular muscularization, and there was statistically positive correlation between the expression of CTGF and cyclinD1. Conclusion CTGF and cyclinDl expressions significantly were upregulated in pulmonary arteries from rats exposed to cigarette smoke （2-8w） and there was a significant positive correlation between their expressions. Their expression variations may be associated with abnormal proliferation of pulmonary artery smooth muscle cells induced by cigarette smoke.

关 键 词：细胞周期蛋白D1 烟雾吸入损伤 肌 平滑 血管 结缔组织生长因子 

分 类 号：R363[医药卫生—病理学]