原发性胆汁性肝硬化患者共刺激分子B7-H4的检测及临床意义  

Expression of costimulating factor B7-H4 in patients with primary binary cirrhosis

作　　者：赵臣[1] 李永哲[1] 赵阳[2] 胡朝军[1] 刘定华[1] 佟大伟[1] 张蜀澜[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科,100730 [2]中国人民解放军第二二二医院传染科,132012

出　　处：《中华微生物学和免疫学杂志》2008年第9期851-855,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金资助（30471617,30640084）;国家高技术研究发展技划（863计划）重大专项基金资助项目（2002AARTZ2011,2006AA02Z436）

摘　　要：目的探讨原发性胆汁性肝硬化（primary biliary cirrhosis，PBC）患者共刺激因子B7-H4的表达及其与疾病发病机制的关系。方法分别采用荧光实时定量PCR法（real-time PCR）、酶联免疫吸附试验（ELISA）及流式细胞术（FCM）检测65名PBC患者外周血单个核细胞（PBMC）B7-H4 mRNA表达水平、血清IL-2水平以及CD4^＋、CD8^＋T细胞亚群和T细胞表面B7-H4表达百分率，同时监测抗线粒体抗体（anti-mitochondrial antibody，AMA）及临床各项生化指标的关系。结果（1）PBC患者PBMC B7-H4 mRNA水平及T细胞表面B7-H4表达百分率显著低于非PBC肝硬化组及健康对照组（P〈0．01）。（2）活化72h后各实验组及对照组IL-2含量及CD4^＋、CD8^＋、CD4^＋CD8^＋T淋巴细胞表达水平均低于活化前，以非PBC肝硬化组与健康对照组降低显著（P〈0．05）；PBC组IL-2含量及CD4^＋、CD4^＋CD8^＋T淋巴细胞表达水平高于非PBC肝硬化组与健康对照组（P〈0．01）。（3）AMA-M2阳性患者血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALP）及γ-谷氨酰转肽酶（GGT）水平升高，其中ALP及GGT升高显著（P〈0．05）；AMA—M2阳性患者与阴性患者T细胞表面B7-H4表达百分率差异无统计学意义（P〉0．05）。结论共刺激因子B7-H4对PBC患者体内T细胞活化增殖及细胞因子分泌的抑制作用减弱，为研究PBC的发生发展和阐明PBC的发病机制提供了试验资料。Objective To study the relationship between the expression of costimulating factor BT- H4 in patients with primary biliary cirrhosis （PBC） and the pathogenesis of PBC. Methods The expression of B7-H4 mRNA on peripheral blood mononuclear cell （PBMC） of 65 patients with PBC was tested by realtime PCR. Serum levels of IL-2 were assayed by ELISA. CD4^ ＋ , CD8^ ＋ T lymphocytes expression level and B7-H4 expression rate before and after activation were measured by three-color flow cytometry （FCM）. Resuits （ 1 ） Expression of B7-H4 mRNA and BT-H4 percentage in PBC group were significantly lower than that in none-PBC group and healthy controls （ P 〈 0.01 ） ; （ 2 ） After 72 h activation, the percentage of CD4^＋ , CD8 ^＋ , and CD4 ^＋ CD8 ^＋ T lymphocytes and serum levels of IL-2 decreased （ P 〈 0.05 ）, and the percentage of CD4 ^＋ , CD4 ^＋ CD8 ^＋ T lymphocytes and serum levels of IL-2 were significantly higher than that of none- PBC group and healthy controls （P 〈 0.01 ） ;（ 3 ） Levels of alanine aminotransferase （ALT）, aspartate aminotransferase（ AST）, alkaline phosphatase（ALP） and γ-glutamyl transpeptidase（GGT） of patients with posi- tive anti-mitochondrial antibody（AMA）-M2 rose. There was no significant difference of BT-H4 expressions on T cells between patients either with or without AMA-M2 antibody. Conclusion The costimulating factor BT-H4 can express on T lymphocytes which is activated by phytohemagglutinin（PHA） and plays a negative role on T cells responses.

关 键 词：原发性胆汁性肝硬化 外周血单个核细胞 共刺激因子 B7-H4 抗线粒体抗体 

分 类 号：R575.2[医药卫生—消化系统] R392.11[医药卫生—内科学]