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

摘要

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 test-ed 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 veloci-ty (E), FEF75(P<0. 01, P<0. 05). There were positive correlations between AI and left ventricular diastolic di-ameter (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.%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。