细颗粒物加重吸烟大鼠肺组织损伤及间隙连接蛋白43表达研究  

Connexin 43 expression and lung tissue damage in rats under combined chronic smoking and PM_(2.5) exposure

作　　者：胡建荣[1,2] 许华俊[2] 李庆云[2] 李春雷 孙娴雯[2] 张秀娟[2] 

机构地区：[1]上海交通大学医学院附属仁济医院嘉定分院呼吸科,上海201800 [2]上海交通大学医学院附属瑞金医院呼吸科,上海200025 [3]复旦大学环境科学与工程系,上海200433

出　　处：《内科理论与实践》2016年第6期380-385,共6页Journal of Internal Medicine Concepts & Practice

基　　金：上海市嘉定区卫生局科研基金(项目编号:2013-KY-004);上海市科学技术委员会科研计划项目(项目编号:10231203902)

摘　　要：目的 :探讨间隙连接蛋白43(connexin 43,Cx43)在短期细颗粒物(PM_(2.5))暴露加重被动吸烟大鼠肺组织损伤中的作用。方法:28只雄性Wistar大鼠随机分为对照组、单纯被动吸烟组、低剂量PM_(2.5)暴露组(浓度1.25 g/L)和高剂量PM_(2.5)暴露组(浓度5 g/L),每组各7只。在最后一次PM_(2.5)暴露24 h后,测定大鼠肺功能;收集支气管-肺泡灌洗液(BALF),测定BALF上清中白介素(IL)-6、丙二醛(MDA)、总抗氧化能力(T-AOC)、谷胱甘肽过氧化物酶(GSHPx)和过氧化氢酶(CAT);取左肺上叶肺组织行Cx43蛋白免疫组织化学检测。结果:在对照组、单纯被动吸烟组、低剂量PM_(2.5)暴露组和高剂量PM_(2.5)暴露组4组中,0.3 s用力呼气量与用力肺活量的比值(FEV_(0.3)/FVC)依次下降(均P<0.05),BALF中MDA及IL-6水平则依次升高(均P<0.05),而T-AOC、GSH-Px和CAT水平也依次下降(P<0.05)。肺组织Cx43显示为棕黄色颗粒,对照组含量最多,单纯被动吸烟组次之,PM_(2.5)暴露组明显减少,且PM_(2.5)高浓度组较低浓度组进一步减少。Cx43的积分光密度值(IOD)与IL-6、MDA呈负相关(均P<0.01),与GSH-Px、CAT、FEV_(0.3)/FVC呈正相关(均P<0.01)。结论:PM_(2.5)暴露可使Cx43蛋白表达发生明显改变,使气道炎症和氧化应激水平上调,进而使大鼠肺功能出现明显下降。Objective To study the role of connexin 43 （Cx43） in aggravation of smoking induced lung tissue damage by short-term PMz5 exposure in rats. Methods Twenty-eight male Wistar rats were randomly divided into 4 groups （7 rats in each group）： control group, smoking group, low-dose PMzs exposure group （0.3 mL, 1.25 g/L）, and high-dose PM2.5 expo- sure group （0.3 mL, 5 g/L）. Rats in smoking group were given passive smoking for 45 d. Rats in PM2.5 exposure group were additionally exposed to PMzs after the last day of passive smoking for 3 d. Lung function tests were performed 24 h after the last PM2.5 exposure. Levels of intedeukin-6 （IL-6）, total antioxidant capacity （T-AOC）, malondialdehyde （MDA）, glu- tathione peroxidase （GSH-Px） and eatalase （CAT） in bronchoalveolar lavage fluid （BALF） were measured, and Cx43 in left upper lung lobe was detected by immunohistochemistry. Results The forced expiratory volume in 0.3 s（FEV0.3）/forced vital capacity （FVC） decreased stepwisely from control group, smoking group, low-dose PM2.5 exposure group to high-dose PM2.5 exposure group （P〈0.01）; MDA and IL-6 increased stepwisely （P〈0.05） and T-AOC, GSH-Px and CAT decreased stepwise- ly （P〈0.05）. Immunohistochemically, Cx43 appeared as brown granules in lung tissue. It was decreased stepwisely from control group, smoking group, low-dose PM2.5 exposure group to high-dose PM2.5 exposure group （P〈0.05）. The integrated optical density （IOD） value of Cx43 was negatively correlated with IL-6, MDA （all P〈0.01）, and positively related with GSH-Px, CAT, and FEV0.3/FVC （all P〈0.01）. Conclusions Exposure to PM2.5 could decrease the expression of Cx43, up-regulate the smoking-induced airway inflammation, and thereby worsening the lung function.

关 键 词：细颗粒物 炎症 氧化应激 肺功能 间隙连接蛋白43 

分 类 号：R56[医药卫生—呼吸系统]