烟雾暴露对大鼠肺血管重塑及TLR-4表达的影响  

Effects of smoking exposure on pulmonary vascular remodeling and the expression of TLR-4 in rats

作　　者：王萍[1] 彭红星[1] 曾玉兰[1] 熊玮[1] 周薇[1] WANG Ping;PENG Hong-xing;ZENG Yu-lan;XIONG Wei;ZHOU Wei(Department of Respiratory Medicine,LiYuan Hospital,Huazhong University of Science and Technology,Wuhan 430077,China)

机构地区：[1]华中科技大学附属梨园医院呼吸内科,湖北省武汉市430077

出　　处：《实用老年医学》2018年第8期717-720,725,共5页Practical Geriatrics

基　　金：华中科技大学自主创新基金资助项目(2015QN027)

摘　　要：目的观察烟雾暴露对大鼠肺血管重塑及Toll样受体(TLR)-4表达的影响,并探讨其可能的作用机制。方法 SD系清洁级雄性健康大鼠40只,随机分为对照组(S1),烟雾暴露4周组(S2),烟雾暴露8周组(S3),烟雾暴露12周组(S4),每组各10只。用HE染色观察肺血管形态学变化,测量各组大鼠肺血管管壁面积/血管总面积比值(WA%),血管壁厚度/血管外径比值(WT%)。用免疫组织化学染色法检测TLR-4蛋白、肺血管平滑肌增殖细胞核抗原(PCNA)蛋白在肺血管中的表达。结果 S2、S3和S4组WA%、WT%均明显高于S1组,且与烟雾暴露时间呈正比,各组间差异均具有统计学意义(P<0.05);随烟雾暴露时间延长,4组间TLR-4蛋白、PCNA蛋白水平呈时间依赖性增加,任意相邻2组间差异具有统计学意义(P<0.05);TLR-4蛋白水平与WA%、WT%、PCNA均呈正相关(r=0.815,0.769,0.713,P<0.01)。结论烟雾暴露可上调TLR-4蛋白的表达,诱导肺血管平滑肌细胞增殖,这可能是烟雾暴露引起肺血管重塑的机制之一。Objective To observe the expression of Toll-like receptor 4（ TLR-4） in pulmonary vessel induced by smoking exposure in rats,and to explore the possible mechanism of pulmonary vascular remodeling. Methods Forty male healthy and clean rats of SD level were randomly divided into S1 group（ no smoking exposure）,S2 group（ receiving smoking exposure for 4 weeks）,S3 group（ receiving smoking exposure for 8 weeks）,S4 group（ receiving smoking exposure for 12 weeks）,with 10 rats in each group. HE staining was used to observe the morphological changes of pulmonary artery. The proportion of pulmonary artery wall area/total vascular area（ WA%） and pulmonary artery wall thickness/vascular external diameter（ WT%） were measured by medical image analysis system. The expression of TLR-4 in pulmonary artery was measured by immunohistochemical staining. Results WA%,WT% in S2 group,S3 group and S4 group were significantly higher than those in S1 group（ P〈0. 05）,and all were positively correlated with the time of smoking exposure. With the increase of smoking exposure time,the levels of TLR-4 protein and pulmonary vascular smooth muscle cell nuclear antibody（ PCNA） protein increased（ P〈0. 05）; The expression of TLR-4 protein was positively correlated with WA%,WT% and PCNA protein（ r = 0. 769,0. 815,0. 713,P〈0. 01）. Conclusions Smoking exposure can up-regulate the expression of TLR-4 protein and induce the proliferation of pulmonary vascular smooth muscle cells,which may be one of the mechanisms of pulmonary vascular remodeling in smoking rats.

关 键 词：烟雾暴露 TOLL样受体4 平滑肌增殖细胞核抗原 肺血管重塑 

分 类 号：R563[医药卫生—呼吸系统]