佐剂性关节炎大鼠心肺功能损伤与TGF-β1/Smad2、4、7通路的关系  

Relations of cardiopulmonary dysfunction and TGF-β1 /Smad2,4,7 pathway in rats of adjuvant arthritis

作　　者：黄传兵[1] 万磊[1] 刘健[1] 李明[2] 纵瑞凯[1] 曹云祥[1] 朱艳[3] 

机构地区：[1]安徽中医药大学第一附属医院风湿病科,合肥230031 [2]安徽中医药大学研究生部,合肥230038 [3]安徽中医药大学第二附属医院,合肥230000

出　　处：《安徽医科大学学报》2014年第7期901-905,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81173211);国家科技支撑计划(编号:2012BA126B02);国家中医药重点学科中医痹病学建设项目(编号:国中医药发[2009]30号);安徽省科技厅科研计划项目(编号:09020304046);安徽省卫生厅中医药科研项目(编号:2009ZY05);安徽现代中医内科应用基础与开发研究省级实验室建设项目(编号:科条[2008]150号);安徽中医学院科技创新团队项目(编号:2010TD005);安徽省115"新安医药研究与开发"创新团队

摘　　要：目的研究佐剂性关节炎(AA)大鼠心肺功能变化与转化生长因子β1(TGF-β1)/Smad2、4、7通路的关系。方法将30只大鼠随机均分为正常对照组和模型组,向模型组大鼠右后足跖皮内注射弗氏完全佐剂0.1 ml致炎,复制成AA模型。致炎19 d后,观察大鼠足跖肿胀度、关节炎指数(AI),采用超声诊断仪检测大鼠心功能、小动物肺功能仪检测肺功能变化,免疫印迹法检测大鼠心肺TGF-β1、Smad2、Smad4、Smad7蛋白表达。结果与正常对照组比较,模型组大鼠足趾肿胀度、AI升高,心肺功能降低,心肺组织TGF-β1、Smad2、Smad4蛋白表达升高,Smad7降低(P<0.01,P<0.05);相关性分析显示,足趾肿胀度与75%肺活量的最大呼气流量(FEF75)呈负相关,AI与左房舒张末期内径(LA)呈正相关,与用力最大呼气流量(MFEF)呈负相关,TGF-β1与左心室短轴缩短率(FS)、50%肺活量的最大呼气流量(FEF50)呈负相关,Smad2与左室舒张末期内径(LV)呈正相关,Smad4与舒张早期峰值流速(E峰)、FEF75呈负相关,Smad7与FEF75、MFEF呈正相关(P<0.01,P<0.05)。结论AA大鼠心肺功能损伤可能与TGF-β1/Smad2、4、7信号通路过度激活有关。Objective To study the changes of cardiopulmonary function and transforming growth factor beta1 （TGF-β1）/Smad2, 4, 7 pathway in rats of adjuvant arthritis （AA）. Methods Thirty rats were randomly divided into normal control group and model group. The model group was intracutaneously injected with 0. 1 ml of Freund’ s complete adjuvant in the right hindlimb. After nineteen days of inflammatory-induction, paw swelling and arthritis index （ AI） were observed cardiac function was tested using ultrasonic diagnostic, and pulmonary function was tested using small animal spirometer. The expressions of TGF-β1, Smad2, Smad4, Smad7 protein were detected by Western blot. Results Compared with normal control group, paw swelling, AI, TGF-β1, Smad2, Smad4 protein were increased, and cardiopulmonary function parameters, cardiopulmonary, Smad7 protein were decreased in rats of AA （ P〈0. 01 , P〈0. 05 ） . There were negative correlations between paw swelling and 75% of vital capacity maximum expiratory flow （ FEF75 ） , AI and maximum forced expiratory flow （ MFEF ） , TGF-β1 and fractional shortening （ FS） , 50% of vital capacity maximum expiratory flow （ FEF50 ） , Smad4 and peak early diastolic velocity （E）, FEF75（P〈0. 01, P〈0. 05）. There were positive correlations between AI and left ventricular diastolic diameter （LV）, Smad2 and left atrial diastolic diameter（LA）, Smad7 and FEF75, MFEF （P〈0. 01, P〈0. 05）. Conclusion Heart and lung function impairment may be associated with excessive activation in signaling pathways of TGF-β1/Smad2,4,7 in AA.

关 键 词：佐剂性关节炎 心功能 肺功能 SMAD通路 转化生长因子 

分 类 号：R392.12[医药卫生—免疫学] R392-33[医药卫生—基础医学]