重组人肿瘤坏死因子受体融合蛋白体外对佐剂性关节炎大鼠T淋巴细胞功能的影响  

Effect of rhTNFR: Fc on T lymphocytes from rats with adjuvant arthritis

作　　者：吴华勋[1] 陈镜宇[1] 汪庆童[1] 刘丽华[1] 吴育晶[1] 宋姗姗[1] 黄蓓[1] 常艳[1] 张玲玲[1] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药理学教育部重点实验室,合肥230032

出　　处：《安徽医科大学学报》2012年第11期1324-1328,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30973543、81173075);安徽省高校自然科学基金(编号:KJ2011Z181、KJ2011Z180);安徽省自然科学基金(编号:1208085QH146)

摘　　要：目的研究重组人肿瘤坏死因子受体融合蛋白(rhT-NFR:Fc)体外用药对佐剂性关节炎(AA)大鼠T淋巴细胞增殖及T细胞亚群比例的影响。方法完全弗氏佐剂(CFA)免疫SD大鼠诱导AA模型,分离培养胸腺及肠系膜淋巴结淋巴细胞,rhTNFR:Fc(10、1、0.1、0.01、0.001μg/ml)体外给药,氚标记的胸腺嘧啶核苷(3H-TdR)掺入法检测rhTNFR:Fc对胸腺T淋巴细胞增殖的影响,流式细胞术检测总Th细胞(CD4+/CD3+)、活化Th细胞(CD4+/CD25+)、CD4+/CD25+/Foxp3+Treg细胞及CD4+/CD62L+未活化Th细胞比例。结果 rhTNFR:Fc组能不同程度的抑制胸腺T淋巴细胞的异常增殖,对CD4+/CD3+总Th细胞比例无显著影响,可以明显降低异常活化的CD4+/CD25+Th细胞比例(P<0.01,P<0.05),明显提高下降的CD4+/CD25+/Foxp3+Treg细胞、CD4+/CD62L+未活化Th细胞比例(P<0.05,P<0.01)。结论 rhTNFR:Fc对AA大鼠的治疗作用可能与其抑制T淋巴细胞增殖、调节T细胞亚群比例有关。Abstract Objective To investigate the effects of rhTNFR ： Fc on the proliferation and differentiation of T lympho- cytes from adjuvant arthritis （AA） rats. Methods AA rats were induced by complete Freund adjuvant, and thy- mocytes and T lymphocytes in lymph nodes were collected and incubated. RhTNFR： Fc （10,1,0. 1,0. 01,0. 001μg/ml） was added into the T lymphocytes suspension. Results RhTNFR： Fc could inhibit T lymphocytes prolifer- ation, down-regulated CD4^＋ CD25^＋ T cells and up-regulated unactived CD4^＋ CD62L^＋ T cells, CD4 ^＋/CD25^＋ / Foxp3^＋ Treg, but had no obvious effect on the percentage of CD3^＋ CD4^＋ T cells. Conclusion Our results indicate that rhTNFR： Fc significantly inhibits T lymphocytes proliferation and regulates T lymphocytes subtype, which might be one of the therapeutic mechanisms for rhTNFR： Fc.

关 键 词：佐剂性关节炎 T淋巴细胞 肿瘤坏死因子-Α 重组人肿瘤坏死因子受体融合蛋白 增殖 

分 类 号：R965.1[医药卫生—药理学] R593.2[医药卫生—药学]