新风胶囊对佐剂关节炎大鼠肺功能及Notch信号传导通路的影响

Effects of Xinfeng Capsule on Pulmonary Function and Notch Signaling Pathway in Adjuvant Arthritis Rats

目的:观察新风胶囊对佐剂关节炎(AA)大鼠足跖肿胀度(E)、关节炎指数(AI)、肺系数(LI)、肺功能变化、调节性T细胞(Treg)及肺组织Notch受体、配体表达的影响。方法:将84只大鼠随机分为正常对照(NC)组、模型(Model)组、甲氨喋呤(MTX)组、雷公藤多苷片(TGT)组和新风胶囊低剂量(XFC-L)组、新风胶囊中剂量(XFC-M)组、新风胶囊高剂量(XFC-H)组,每组12只,分别给动物右后足跖皮内注射弗氏完全佐剂(FCA)0.1mL致炎(除NC组外),致炎后第19d开始给药。NC组及Model组均给予生理盐水,其余5组分别给予MTX、TGT、XFC。观察各组大鼠上述各指标的变化。结果:①与NC组相比,Model组大鼠E、AI、LI在1s内平均呼气流量(FEV1/FVC)、肺泡炎积分、Notch3、Notch4、Delta1表达明显升高(P<0.01);用力肺活量(FVC)、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+T细胞、CD25+T细胞、CD4+CD25+Treg、Notch1、Jagged1、Jagged2表达明显降低(P<0.01)。②与Model组相比,各治疗组大鼠体重、FVC、FEF25、FEF50、FEF75、MMF、PEF、Notch1、Jagged1、Jagged2及Treg的表达升高;E、AI、LI、FEV/FVC及Notch3、Notch4、Delta1的表达降低(P<0.05或P<0.01)。③与XFC-M组相比,其余各治疗组LI、肺泡炎积分及Notch3、Delta1升高;FVC、FEF25、FEF50、FEF75、MMF、PEF及Notch1、Jagged1、CD4+T细胞、CD4+CD25+Treg降低(P<0.05或P<0.01)。结论:AA大鼠存在关节局部的炎症反应和肺功能的降低,通过相关分析得知肺功能降低与Notch信号传导通路的表达有关;新风胶囊能明显改善AA大鼠关节症状和肺功能,可能通过促进Delta1、Notch3、Notch4的表达、抑制Jagged1、Jagged2、Notch1表达,降低炎症反应和免疫复合物沉积,改善关节和肺部症状。

This study observed the effects of Xinfeng Capsule on paw swelling degree （E）, arthritis index （AI）, lung index （LI）, pulmonary function changes, regulatory T ceils （Treg） and Notch receptor and ligand expression of lung tissue in adjuvant arthritis （adjuvant arthritis, AA） rats. 84 rats were randomly divided into the normal control （NC） group, the model （Model） group, the methotrexate （MTX） group, the TWP-chip （TGT） group, the low dose of Xinfeng Capsule （XFC-L） group, the dose of Xinfeng Capsule （XFC-M） group, and the high dose of Xinfeng Capsule （XFC-H） group, 12 rats each group. Except for the NC group, the animals from other groups were given right rear paw intradermal injection of O. 1 mL Freund＇s complete adjuvant （FCA）, which induced inflammation 19 d after administra- tion. The NC group and the Model group were given normal saline, while the other five groups were given MTX, TGT, and XFC. Rats were observed for changes in the indices mentioned above. Compared with the NC group, the Model rats had significantly higher E, AI, LI, 1 seconds, average expiratory flow （FEV1/FVC%）, pulmonary inflammation points, Notch3, Notch4, and Dehal expression（P〈0.01 ）, and significantly lower forced vital capacity （FVC）, 25% lung capacity, peak expiratory flow （FEF25）, 50% lung capacity, peak expiratory flow （FEF50）, 75% lung capacity, peak expiratory flow（FEF75）, maximum mid-expiratory flow rate （MMF）, forced maximal expiratory flow （PEF）, CD4 Treg, CD25＋ Treg, CD4^＋CD25 Treg, Notchl, Jagged1, Jagged2 expression （P〈0.01）. Compared with the Model group, the treatment groups had increased body weight, FVC, FEF25, FEF50, FEF75, MMF, PEF, Notchl, Jaggedl, Jagged2, and the expression of Treg, and lower E, AI, LI, FEV1/FVC, and Notch3, Notch4, Deltal expression （P〈0.05 or P〈0.01）. Compared with the other treatment groups, the XFC-M group had increased LI, alveolitis integral and Notch3, Delta1, and de： creased FVC, FEF25, FEF50 FEF75, MMF, PEF, and Notchl, Jaggedl, CD4^＋Treg, CD4^＋ CD25 Treg （P〈0.05 or P〈0.01）. The results show that the AA rats suffer from joint local inflammatory response and reduced lung function, and the correlation analysis indicates that the reduced lung function may be associated with the expression of the Notch signal transduction pathway; Xinfeng capsule may significantly alleviate the joint symptoms and improve lung function, possibly by promoting Deha1, Notch3 and Notch4 expression, inhibiting Jaggedl, Jagged2, and Notchl expression, reducing inflammation and immune complex deposition, and consequently alleviating joint and lung symptoms.