Th1/Th2/Th17细胞因子及抗心肌抗体在小鼠扩张型心肌病中的表达及其意义  

Expressions and Significance of Th1/Th2/Th17 Cytokines and Antimyocardial Antibodies in Mouse Dilated Cardiomyopathy

作　　者：李丽萍[1] 孔清[1] 赖文盈 潘晓芬[1] 伍伟锋[1] 

机构地区：[1]广西医科大学第一附属医院心内科广西心血管病研究所,广西南宁530021

出　　处：《中国临床医学》2015年第4期447-450,共4页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金资助项目(编号:81160032)

摘　　要：目的:观察Th1/Th2/Th17细胞因子及抗心肌抗体在小鼠扩张型心肌病(dilated cardiomyopathy,DCM)中的表达,并探讨其在DCM发病机制中的作用及意义。方法:用柯萨奇病毒B3(CVB3)建立Balb/c小鼠DCM模型(DCM组);对照组注射磷酸盐缓冲液(PBS)。第24周处死小鼠,采用心肌Masson’s染色法观察心肌组织纤维化程度;应用蛋白芯片检测血浆中Th1、Th2、Th17细胞因子的表达;采用ELISA方法检测小鼠血浆中的抗心肌抗体,如抗线粒体内膜ADP/ATP载体(adenine nucleotide translocator,ANT)抗体、抗β-肌球蛋白重链(β-myosin heavy chain,β-MHC)抗体、抗心肌L型钙通道(cardiac Ltype calcium channel,CACH2)抗体、β1肾上腺素能受体(anti-β1-adrenergic receptor,β1AR)抗体的水平。结果:DCM组在病毒感染24周后的心肌病理检查结果符合DCM特征;与对照组比较,DCM组血浆中白细胞介素(IL)-2、IL-10、IL-13、IL-28及肿瘤坏死因子-α(TNF-α)表达下降,而IL-6、IL-17、IL-21、IL-22、IL-23及转化生长因子-β(TGF-β)的表达均明显升高(P均<0.05)。同时,DCM组小鼠血浆中抗ANT及抗心肌β-MHC抗体较对照组明显升高(P均<0.05);相关性分析结果显示,DCM组小鼠血浆中IL-22水平与抗ANT抗体水平呈正相关(P<0.05)。结论:抗心肌抗体(如抗ANT抗体、抗β-MHC抗体)和Th1/Th2/Th17细胞因子(如IL-2、IL-10、IL-13、IL-28、TNF-α、IL-6、IL-17、IL-21、IL-22、IL-23)及TGF-β失衡导致的免疫紊乱可能在DCM发病中起重要作用,且IL-22可能促进抗ANT抗体的产生。Objective：To observe the expressions of Thl/Th2/Th17 eytokines and antimyocardial antibodies in mouse dilated cardiomyopathy （DCM）, and explore their roles and significance in DCM pathogenesis. Methods： BALB/c mouse model of DCM was built with coxsackievirus（CVB3）. Mice in control group were treated with phosphate-buffered saline （PBS） i. p. Mice were killed at the 24th week, and the fibrosis degree of myocardial tissue was observed by myocardial Masson＇ s staining. Expressions of Thl/Th2/Thl7 cytokines in plasma were detected by using protein microarray. The mouse plasma levels of an- timyocardial antibodies such as adenine nucleotide translocator（ANT） antibody, β-myosin heavy chain（β-MHC） antibody, car- diac L-type calcium ehannel（CACH2）, and anti-β1-adrenergic receptor（β1AR） were measured by enzyme-linked immunosorbent assay （ELISA）. Results： The result of myocardial pathological examination in DCM group fit the features of DCM 24 weeks af- ter virus infection. Compared with those in control group, expression levels of interleukin（IL）-2, IL-10, IL-13, IL-28 and TNF-a in DCM group decreased（P〈0. 05）, however, the expression levels of IL-6, IL-17, IL-21, IL-22, IL-23 and TGF-β in- creased significantly（P〈0. 05）. Meanwhile, compared with those in control group, the plasma levels of ANT and 13-MHC anti- bodies in DCM group increased significantly （P〈0. 05）. Furthermore, positive correlation was found between level of IL-22 and level of anti-ANT according to correlative analysis（P〈0. 05）. Conclusions： Immunologic derangement induced by imbal- ance of antimyocardial antibodies such as ANT and β-MHC, and Th1/Th2/Thl7 cytokines such as IL-2. IL-10. IL-β 、 IL-28. TNF-α.IL-6.IL-17.IL-21 .IL-22.IL-23 and TGF-α may play important roles in the pathogenesis of DCM. Furthermore, IL-22 may boost the production of ANT antibody.

关 键 词：细胞因子 抗心肌抗体 扩张型心肌病 

分 类 号：R542.2[医药卫生—心血管疾病]