新风胶囊通过抑制FAK/PI3K信号通路减轻佐剂性关节炎大鼠肺功能损伤  

Action of alleviated lung function impairment in rats with adjuvant arthritis by inhibiting the FAK/PI3K signaling pathway by Xinfeng Capsules

作　　者：章平衡 刘健[3] 万磊[3] 纵瑞凯[3] 夏金金 江伟强[1] ZHANG Ping-heng;LIU Jian;WAN Lei;ZONG Rui-kai;XIA Jin-jin;JIANG Wei-qiang(Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)

机构地区：[1]南方医科大学珠江医院,广州510282 [2]广州中医药大学第一附属医院,广州510405 [3]安徽中医药大学第一附属医院,合肥230031

出　　处：《中华中医药杂志》2022年第6期3153-3159,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82004102)。

摘　　要：目的:探讨新风胶囊(XFC)对佐剂性关节炎(AA)大鼠肺功能及FAK/PI3K信号通路的影响。方法:将SPF级SD大鼠随机分为正常(NC)组、模型(MC)组、雷公藤多苷(TPT)组、新风胶囊(XFC)组。除NC组外,其余组采用弗氏完全佐剂建立AA模型,第30天开始给药,每天1次,连续30 d。采用肺功能仪检测大鼠肺功能参数,HE染色观察大鼠肺组织病理形态学变化,ELISA检测血清白细胞介素(IL)-6、IL-8、IL-27、转化生长因子-β1(TGF-β1)水平,RT-qPCR检测肺组织肺组织ColⅠα、ColⅢmRNA水平,Western Blot法检测肺组织PI3K、p-PI3K、FAK、p-FAK蛋白水平,免疫组织化学染色法观察肺组织PI3K、FAK蛋白的表达。结果:与NC组比较,MC组大鼠肺功能参数FVC、FEF25、FEF50、FEF75、PEF显著降低(P<0.01),肺组织ColⅠα、ColⅢmRNA及IL-6、IL-8、TGF-β1、p-PI3K、p-FAK表达显著升高(P<0.05,P<0.01),IL-27显著降低(P<0.01);与MC组比较,XFC组和TPT组FVC、PEF25、FEF50、FEF75、PEF均显著升高(P<0.01),ColⅠα、ColⅢmRNA及p-PI3K、p-FAK表达显著降低(P<0.05,P<0.01);XFC组细胞因子IL-8、TGF-β1表达量降低,IL-27表达升高(P<0.05,P<0.01);而TPT组IL-6、IL-8、TGF-β1降低,IL-27升高(P<0.05,P<0.01);与TPT组比较,XFC组肺功能参数FEF75显著升高(P<0.01),ColⅠα、ColⅢmRNA及IL-8、TGF-β1、p-PI3K、p-FAK表达显著降低(P<0.05,P<0.01)。XFC组大鼠肺组织炎症细胞明显减少,胶原纤维蛋白沉积减少,肺间隔缩窄,肺泡腔较完整。结论:XFC可能通过调节细胞因子的表达水平调控FAK/PI3K信号通路活化,改善RA肺功能损伤。Objective:To observe the effect of Xinfeng Capsules(XFC)on lung function and FAK/PI3K pathway in adjuvant arthritis(AA)rats.Methods:SPF grade SD rats were randomly divided into normal(NC),model(MC),XFC,and TPT group.Except the NC group,the other three groups were induced into AA models with complete Freund’s adjuvant(CFA),the rats were inistrated from day 30 after the injection of CFA by gavage,once a day for 30 days.Pulmonary function was observed by lung function instrument.The pathological changes of lung tissue was observed by HE staining.The levels of IL-6,IL-8,TGF-β1 and IL-27 were detected by ELISA.ColⅠα,ColⅠαmRNA were detected by RT-qPCR.The levels of PI3K,p-PI3K,FAK,p-FAK proteins were determined by Western Blot analysis.The expression and distribution of FAK and PI3K in the lung tissues were analyzed by immunohistochemical staining.Results:Compared with NC group,lung function parameters FVC,FEF25,FEF50,FEF75 and PEF of rats in MC group were decreased(P<0.01),the expression of ColⅠα,ColⅠαm RNA,IL-6,IL-8,TGF-β1 and the proteins of p-PI3K,p-FAK were increased in MC rats(P<0.05,P<0.01),while the expression of IL-27 decreased(P<0.01).Compared with MC group,lung function parameters FVC,FEF25,FEF50,FEF75 and PEF were increased in XFC group and TPT group(P<0.01),the expression of ColⅠα,ColⅠαmRNA,p-PI3K and p-FAK were decreased in XFC group and TPT group(P<0.05,P<0.01).The expression of IL-8 and TGF-β1 in XFC group were decreased,while IL-27 were increased(P<0.05,P<0.01).The expression of IL-6,IL-8 and TGF-β1 in TPT group were decreased,while IL-27 was increased(P<0.05,P<0.01).Compared with TPT group,lung function parameters FEF75 were increased(P<0.01),the expression of ColⅠα,ColⅠαmRNA,IL-8,TGF-β1,p-PI3Kand p-FAK were decreased in XFC group(P<0.05,P<0.01).For the XFC group rats,both the inflammatiry cells in the lung tissue of the rats and the deposition of collagen fibrin reduced significantly.Meanwhile,the pulmorary septum were narrowed,while the alveolar cavity was relatively i

关 键 词：佐剂性关节炎 肺功能 FAK/PI3K信号通路 细胞因子 新风胶囊 动物模型 类风湿关节炎 

分 类 号：R285.5[医药卫生—中药学]