新风胶囊通过BTLA-HVEM诱导Treg免疫耐受改善膝骨关节炎大鼠心肺功能  

Xinfeng Capsule improves cardiopulmonary function of knee osteoarthritis rats by BTLA-HVEM signaling pathway to induce Treg immune tolerance

作　　者：程园园[1] 刘健 冯云霞[1] 刘磊[1] 万磊[2,3] 

机构地区：[1]安徽中医学院研究生部,安徽合肥230031 [2]第一附属医院风湿科,安徽合肥230031 [3]湖北中医药大学研究生部,湖北武汉430065

出　　处：《细胞与分子免疫学杂志》2012年第11期1133-1137,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81173211);国家中医药重点学科中医痹病学建设项目(国中医药发[2009]30号);安徽省科技厅科研计划项目(09020304046);安徽省卫生厅中医药科研项目(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,科条[2008]150号;安徽中医学院科技创新团队项目(2010TD005)

摘　　要：目的:观察膝骨关节炎(KOA)大鼠心肺功能的变化及新风胶囊(XFC)对其影响,探讨可能的分子机制。方法:按随机数字表将40只大鼠随机分为正常对照(NC)组,模型对照(MC)组,氨基葡萄糖对照(GS)组,XFC组,每组10只。除NC组外,采用关节腔注射木瓜蛋白酶和L-半胱氨酸方法复制成KOA大鼠模型,造模后第14天开始给药。NC组及MC组均给予生理盐水,剂量为0.01 g/kg,其余2组分别给予GS、XFC混悬液,剂量分别为0.098 g/kg、0.375 g/kg。采用超声诊断仪检测大鼠心功能,动物肺功能仪检测大鼠肺功能,ELISA法检测BTLA、HVEM、IL-17、IL-4、TGF-β1;流式细胞术检测大鼠外周血CD4+CD25+Treg、CD4+CD25+Foxp3+Treg的表达。结果:与NC组比较,MC组体质量、E、E/A、FVC、FEV1、FEF25、FEF50、FEF75、MMF、PEF,BTLA、HVEM、IL-4、CD4+CD25+Treg、CD4+CD25+Foxp3+Treg明显降低,TGF-β1、IL-17明显升高(P<0.01或P<0.05)。与MC组比较,各组大鼠体质量,心功能参数E峰、E/A,肺功能参数FEV1、FEF50、FEF75、PEF,BTLA、HVEM、IL-4、CD4+CD25+Treg、CD4+CD25+Foxp3+Treg明显升高,关节软骨Mankin评分、心系数、肺系数、TGF-β1、IL-17明显降低(P<0.01或P<0.05);与GS组相比,XFC组体质量、Treg升高最为明显(P<0.01或P<0.05)。结论:新风胶囊改善KOA大鼠关节软骨Mankin评分,改善其心肺功能,其机制可能是促进BTLA-HVEM负调共刺激信号作用,诱导Treg免疫耐受,上调IL-4表达,下调IL-17、TGF-β1表达,抑制异常免疫炎症反应。AIM： To observe the effects of Xinfeng Capsule （XFC） on cardiopulmonary function of knee osteoar- thritis （KOA） rats and explore its molecular mechanism. METHODS： Forty rats were randomly divided into normal control （ NC ） group, model control （ MC ） group, glucosamine control （GS） group and XFC group, 10 in each group. All rats were induced to KOA by injected papain and L-Cys into the right knee joint except NC group. Fourteen days after modeling, NC and MC groups were given normal saline （0.01 g/kg）, GS and XFC groups were given glucosamine （0.098 g/kg） and XFC suspension （0.375 g/kg）, respectively. Cardiac and pulmonary function were detected by ultrasonography and animal spirometry, respec- tively. B and T lymphocyte attenuator （ BTLA）, herpesvirus entry mediator （ HVEM）, interleukin （IL）-17, IL-4, transfor- ming growth factor-beta （TGF-β1） were detected by ELISA; CD4＋ CD25＋ Treg and CD4＋ CD25＋ Foxp3＋Treg were detected by flow cytometry. RESULTS： Comparedwith NC group, body mass, levels of early diastolic peak flow velocity （E）, early diastolic peak flow velocity/atrial peak flow velocity （ E/A）, forced vital capacity （ FVC）, forced expiratory volume in ] second （ FEV1 ）, 25% forced expira- tory flow （FEF25）, 50% forced expiratory flow （FEF50）, 75% forced expiratory flow （FEF？5）, maximal mid-expirato- ry flow （ MMF）, peak expiratory flow （ PEF）, expressions of BTLA, HVEM, IL-4, CD4＋CD25＋Treg and CD4＋CD25＋ Foxp3＋ Treg significantly decreased, and TGF-β], IL-17 significantly increased, in MC group （ P 〈 0.01 or P 〈 0. 05）. Compared with MC group, weight, levels of E, E/A, FEV], FEF50, FEF？5, PEF, BTLA, HVEM, IL-4, CD4＋ CD＋25＋ Treg and CD4 ＋ CD25 ＋ Foxp3 ＋ Treg significantly increased, and Mankin score, cardiacindex （ CI ）, lung index （ LI ）, TGF-β1, IL-17 significantly decreased in GS and XFC groups （ P 〈 0. 01 or P 〈 0.05） ; Compared with GS group, weight and

关 键 词：骨关节炎 心肺功能 B T淋巴细胞弱化因子 调节T细胞 新风胶囊 

分 类 号：R292-33[医药卫生—民族医学] R593.21[医药卫生—中医学]