摘要
目的 研究可溶性重组人肿瘤坏死因子受体融合蛋白 (rhu TNFR Fc)对大鼠佐剂性关节炎的治疗作用及其初步机制。方法 测非致炎侧继发性足肿胀 ,用ELISA法测血清中IL 1β ,TNF α的水平 ;Griess法测上清NO的含量 ;流式细胞术检测T淋巴细胞亚群 ;L92 9细胞杀伤法、ELISA法检测rhu TNFR Fc对大鼠腹腔巨噬细胞分泌TNF α的影响。结果 rhu TNFR Fc(0 4 4 ,0 88,1 75mg·kg- 1 )皮下给药对佐剂性关节炎 (AA)大鼠的继发性足肿胀有显著的治疗作用 ,并呈现较明显的剂量依赖性 ,改善AA大鼠多发性关节炎病变症状 ;通过中和TNF α对AA大鼠过高的血清IL 1β、细胞上清NO的产生有明显的抑制作用 (P <0 0 1) ;但对CD4 + T淋巴细胞与CD8+ T淋巴细胞的比值无明显的影响。结论 rhu TNFR Fc有明显的抗炎作用 ,其抗炎作用可能与其中和TNF α,并进一步使IL 1分泌及NO的生成减少有关。
OBJECTIVE: To study the therapeutic effects of rhu-TNFR-Fc on AA and its possible mechanism in rats. METHODS: Wistar rats were immunized with Freund's complete adjuvant and treated with rhu-TNFR-Fc from day 12 to 23 after adjuvant injection. The negative control rats received sterile saline and the positive control group received Dexamethasone. The secondary paw swelling and arthritis index were examined on day 12, 15, 17, 19, 21, 23, 25 and 27 after adjuvant injection. At the termination of the trial (day 28), the content of NO secreted by macrophage in the presence of LPS was assessed and T cell subpopulation in rats were measured by flowing cytometry. ELISA assays were performed to determine serum IL-1β and TNF-α. The activity of TNF-α in the culture supernatant was also measured using L929 cell line or ELISA assays in vitro. RESULTS: rhu-TNFR-Fc (0.44, 0.88, 1.75 mg′kg-1) subcutaneous injection (s.c) significantly inhibited secondary inflammatory reactions(inflammatory swelling and multiple arthritis) in AA rats. Serum IL-1β and NO level were significantly reduced. There was no significant variation in the CD4+/CD8+ ratio. rhu-TNFR-Fc (0.175 - 87.5 μg·mL-1 inhibited the activity of TNF-α in the culture supernatant in vitro. But no difference was observed with ELISA assays. CONCLUSION: The results suggested that rhu-TNFR-Fc may have antiarthritic properties in this experimental model and the mechanisms may be that neutralization of TNF-α reduces the release of cytokines such as IL-1β and other inflammatory mediators such as NO.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2004年第6期435-438,共4页
Chinese Pharmaceutical Journal