4-1BB/4-1BBL在自身免疫性心肌炎小鼠心肌中的表达及意义  

Expression and Significance of 4-1BB/4-1BBL in Experimental Autoimmune Myocarditis

作　　者：郭海鹏[1] 唐其柱[1] 姜明[1] 沈涤非[1] 严玲[1] 邓伟[1] 

机构地区：[1]武汉大学人民医院心内科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2008年第5期563-567,I0001,共6页Medical Journal of Wuhan University

基　　金：高等学校博士学科点专项科研基金(编号:20070486103)

摘　　要：目的:探讨4-1BB/4-1BBL在实验性自身免疫性心肌炎(EAM)小鼠心肌组织中的表达及意义。方法:将提纯的猪心肌肌球蛋白和完全弗氏佐剂等体积混合成乳浊液在1 d、8 d免疫具有遗传易感性的BALB/c小鼠,建立EAM模型。对照组小鼠仅用完全弗氏佐剂皮下注射。分别于初次免疫后21 d、80 d进行心肌炎症评分及血清cTnI测定,采用免疫荧光及RT-PCR技术检测4-1BB/4-1BBL在小鼠心肌组织中的表达。结果:在急性期21 d,模型组小鼠心肌组织见不同程度的急性炎性细胞浸润和心肌细胞变性坏死、cTnI水平高于对照组(P<0.05);80d模型组小鼠心肌组织炎症减弱伴有纤维化出现、cTnI较前期降低;免疫荧光见4-1BBL在模型组心肌中表达明显,在对照组小鼠心肌中少量表达(P<0.05);21 d模型组小鼠心肌组织中4-1BB/4-1BBL基因表达水平均高于对照组(P<0.01),80 d时表达仍然升高(P<0.01)。结论:4-1BB/4-1BBL在EAM小鼠心肌中的表达是上调的,4-1BB/4-1BBL通路参与了自身免疫性心肌炎的发生发展过程。Objective： To establish an animal model of experimental autoimmune myocarditis（EAM） in BALB/c mice and investigate the expression and significance of 4-1BB/4-1BBL in mice EAM. Methods： Cardiac myosin was extracted from porcine ventricular myocardium. Genetically predis posed BALB/c mice were immunized with cardiac myosin covered by complete freund＇s adjuvant （CFA） on day 1 and 8. The control mice were immunized with CFA only. On day21 and 80 after the first immunization, HE staining was used to identify the area of inflammation, serum cTnI was assayed, and the expression of 4 1BB/4-1BBL was measured by immunofluorescence and semi-quantitative RT-PCR. Results： In experimental group, histopathological examination of cardiac tissue showed an obvious inflammatory cell infiltration with myocyte necrosis at day 21, and cTnI was higher than control group. On day 80, fibrosis and a few of inflammatory cells can be observed, cTnI was still higher than control group（P〈0. 05）. No inflammation and fibrosis was found in the myocardiumof control mice. In addition, as compared with those in control group,immunofluorescence and mRNA abundance for both 4-1BB and 4-1BBL were up-regulated at acute phase of the EAM model（P〈0.01）. On day 80, the mRNA abundance was still up-regulated （P 〈0.01）. Conclusion： The expression of 4-1BB and 4-1BBL in myocardium were up-regulated in experimental autoimmune myocarditis. The 4-1BB/4-1BBL pathway maybe plays a role in the occurrence and development of autoimmune myocarditis.

关 键 词：心肌肌球蛋白 4-1BB/4-1BBL 心肌炎 自身免疫 

分 类 号：R542.2[医药卫生—心血管疾病]