新风胶囊对佐剂关节炎大鼠肺功能及Treg、Foxp3、TGF-β1/Smads的作用

Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced arthritis and its mechanism

目的:观察新风胶囊(XFC)对佐剂关节炎(AA)大鼠肺功能、调节T细胞(Treg)及肺组织Foxp3、TGF-β1、Smad3、Smad7的影响。方法:采用弗氏完全佐剂复制AA大鼠模型,致炎后第19天开始给药,将大鼠随机均分为正常对照(NC)组、模型对照(MC)组、甲氨喋呤(MTX)组、雷公藤多苷片(TPT)组和XFC组,给药30 d后,观察各组大鼠足趾肿胀度(E)、关节炎指数(AI)、肺功能、Treg、肺组织病理形态学及肺组织Foxp3、TGF-β1、Smad3、Smad7变化。结果:与NC组相比,MC组大鼠E、AI、肺泡炎积分、TGF-β1及Smad3蛋白表达明显升高(P<0.05或P<0.01);25%肺活量的最大呼气流量(FEF25)、50%肺活量的最大呼气流量(FEF50)、75%肺活量的最大呼气流量(FEF75)、最大呼气中期流量(MMF)、用力最大呼气流量(PEF)、CD4+CD25+Treg及Foxp3、Smad7蛋白表达显著降低(P<0.05或P<0.01)。与MC组相比,XFC组大鼠E、AI、TGF-β1及Smad3表达降低,FEF50、FEF75、MMF、PEF、Treg及Foxp3、Smad7表达升高(P<0.05或P<0.01)。与XFC组相比,MTX组、TPT组大鼠体质量、FEF25、FEF50、FEF75、MMF、Treg降低(P<0.05或P<0.01)。结论:AA大鼠存在关节炎症症状和肺功能降低,XFC能明显抑制AA大鼠足跖肿胀度,降低关节炎症反应,改善肺功能,机制可能是通过上调Foxp3、Treg,下调TGF-β1表达,调节TGF-β1/Smads信号通路传导,改善关节症状和肺功能。

Objective： To investigate the effects of Xinfeng Capsule （XFC） on pulmonary function and related mechanism in adjuvant-induced arthritis （AA） rats. Methods： The rats were randomly divided into five groups ： normal control （ NC ）, model control （ MC ） groups, methotrexate （ MTX ）, tripterygium glycosides tablet （TPT） and Xinfeng capsule （ XFC ）- treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of O. 1 mL Freund＇s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree （E）, arthritis index （AI） ,pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1＇ Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration. Results： Compared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased （ P 〈 0. 05 or P 〈0. 01 ） ; maximum expiratory flow 25% of vital capacity （ FEF25 ） ,50% maximal expiratory vital capacity flow （ FEF50 ）, maximum expiratory flow at 75% of vital capacity （ FEF75 ）, maximum mid-expiratory flow （MMF） ,force peak expiratory flow （PEF）, CD4 ＋ CD25 ＋ Treg,Foxp3 and Smad7 were significantly decreased in MC group （P 〈0.05 or P 〈0.01 ）. Compared to MC group, the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEFb0, FEF75＇ MMF, PEF, Treg,Foxp3 and Smad7 were elevated in XFC group （P 〈0.05 or P 〈0.01 ）. Compared to XFC group, the level of body mass, FEF25, FEF50＇ FEF75＇ MMF and Treg were lower in MTX and TPT groups （ P 〈 0. 05 or P 〈0.01）. Conclusions： There are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.