非诺贝特通过调节Th1/Th2细胞因子的平衡改善自身免疫性心肌炎  

Fenofibrate ameliorates experimental autoimmune myocarditis through modulating the balance of Th1/Th2 cytokines

作　　者：王焱[1,2] 黄明山[1] 李刚[2] 常贺[2] 

机构地区：[1]福建医科大学协和临床医学院,福州350108 [2]厦门大学附属中山医院厦门心脏中心,361004

出　　处：《免疫学杂志》2013年第2期110-114,共5页Immunological Journal

基　　金：国家自然基金资助项目(81270294);福建省自然基金项目(2012J01415);厦门市科技计划项目(3502Z20124054;3502Z20126014)

摘　　要：目的探讨非诺贝特(fenofibrate)对自身免疫性心肌炎(EAM)大鼠的治疗作用。方法将提纯精制后的猪心室肌球蛋白加等体积含灭活的结核杆菌的完全弗氏免疫佐剂充分混匀后,于Lewis大鼠双后足皮下注射制作大鼠EAM模型。于第0天免疫后,非诺贝特组给予非诺贝特灌胃,EAM组给予生理盐水灌胃。免疫后的第17天,超声检测大鼠心功能,处死大鼠取心脏评估心肌炎的严重程度及心体质量比,HE染色,应用实时定量PCR检测心脏的IFN-γ,IL-2,IL-4和IL-10的mRNA表达水平,并进一步通过ELISA检测血清中IFN-γ和IL-4的表达水平。结果非诺贝特组大鼠的心功能指标与EAM组相比得到了显著改善。非诺贝特治疗组的心体质量比和心肌的炎症浸润程度也比EAM模型组有明显的降低。另外,非诺贝特治疗组降低了Th1的细胞因子(IFN-γ,IL-2)的表达并增加了Th2细胞因子(IL-4,IL-10)的表达。ELISA的结果也显示非诺贝特治疗组血清中IFN-γ的水平降低而IL-4的水平升高。结论非诺贝特治疗可能通过调节Th1/Th2细胞因子的平衡改善自身免疫性心肌炎。This study was designed to explore the therapeutical effects of fenofibrate on experimental autoimmune myocarditis(EAM).EAM model was constructed by injection of porcine cardiac myosin and complete Freund’s adjuvant in two hind-limbs of Lewis rats.Fenofibrate or physiological saline was administered orally from day 0(D0) to day 17(D17) on EAM rats.On day 17,cardiac function was examined by echocardiography and the severity of myocarditis was evaluated by hematoxylin and eosin(HE) staining.Furthermore,the mRNA expression of Th1-type cytokines(IFN-γ and IL-2) and Th2-type cytokines(IL-4,IL-10) were determined by quantitative RT-PCR,while the serum levels of IFN-γ and IL-4 were measured by ELISA.We found that cardiac function was improved in fenofibrate treated group as compared to EAM group.Furthermore,heart weight/body weight and the degree of inflammation in heart were significantly lower in fenofibrate treated group than those in EAM group.In addition,treatment with fenofibrate decreased the expression of Th1-type cytokines(IFN-γ,IL-2) but increased the expression of Th2-type cytokines(IL-4 and IL-10).In conclusion,fenofibrate may ameliorate EAM through modulating the balance of Th1/Th2 cytokine.

关 键 词：非诺贝特 TH1/TH2细胞因子 自身免疫性心肌炎 

分 类 号：R542.21[医药卫生—心血管疾病]