抗死亡受体DR5抗体对大鼠佐剂型关节炎的作用机理探讨  

The study of anti-DR5 McAb on rats adjuvant arthritis and its mechanisms

作　　者：李文珠[1] 陶惠然[2] 庄国洪[2] 胡庆中[2] 王生育[2] 陈彩霞[1] 

机构地区：[1]厦门大学医学院生命科学学院,361005 [2]厦门大学医学院抗癌研究中心,361005

出　　处：《中华微生物学和免疫学杂志》2007年第7期651-655,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的研究抗-DR5 McAb对大鼠佐剂型关节炎(AA)的作用及其免疫机理。方法注射弗式完全佐剂建立AA大鼠模型,尾静脉注射抗-DR5 McAb,观察大鼠关节肿胀度、血清和滑膜液中炎症细胞因子IL-1β、TNF-α、IFN-γ水平的变化。RT-PCR检测各组织器官、滑膜和淋巴细胞中DR5 mRNA水平的表达,Western blot分析各组织器官中凋亡相关因子caspase-8、Bcl-2蛋白的表达。结果抗-DR5 McAb能缓解AA病情,使关节肿胀度降低;血液和滑膜组织细胞产生IL-1β、TNF-α、IFN-γ水平下降,抑制滑膜细胞和淋巴细胞的过度增殖。各组织器官中caspase-8蛋白水平上升,Bcl-2蛋白水平下调。结论抗-DR5 McAb能用于大鼠AA的治疗,其治疗机制与细胞表面DR5 mRNA的表达、细胞因子IL-1β、TNF-α、IFN-γ水平和caspase-8、Bcl-2蛋白表达相关。Objective To study the therapeutic effects of anti-DR5 McAb on treating rats adjuvant arthritis（AA） and its immunoregulatory mechanisms. Methods AA was induced by CFA in rats. The rats were injected subcutaneously with anti-DR5 McAb. The volume of rat hind paw was measured before and after injection of Freund＇s complete adjuvant （FCA）. The pathological changes of inflammatory knee joints were observed under optical microscope. DR5 mRNA in serum and liquid of synovial membrane tissue cells was detected by RT-PCR. Caspase-8, Bcl-2 expression of all tissues were analyzed by Western blot. Results The current work shows that anti-DR5 McAb could ameliorate arthritie symptoms. IL-1β、TNF-α、IFN-γconcentrations significantly decreased in AA rats sera and joint fluids after treatment with anti-DR5 McAb. Caspase-8 level raised and Bcl-2 level declined. Conduslon Anti-DR5 McAb exerted anti-inflammatory role by suppressing inflammatory cytokine production. The mechanisms of treatment are related with the expression of DR5 mRNA on cell membrane, the level of cytokine of IL-1β、TNF-α and IFN-γ, protein expression of caspase-8 and Bcl-2.

关 键 词：抗-DR5 McAb 佐剂型关节炎 细胞凋亡 

分 类 号：R593.2[医药卫生—内科学]