重组人肿瘤坏死因子受体融合蛋白治疗大鼠佐剂性关节炎的作用及对巨噬细胞功能的影响

Therapeutic effect of RhTNFR:Fc on rats with adjuvant arthritis and its effect on peritoneal macrophages

目的:研究重组人肿瘤坏死因子受体融合蛋白(RhTNFR:Fc)对佐剂性关节炎(AA)大鼠模型的治疗作用及对巨噬细胞产生细胞因子的影响。方法:完全弗氏佐剂免疫SD大鼠诱导AA模型,随机分为正常组、模型组、RhTNFR:Fc低、中、高剂量组(1,3,9 mg.kg-1)和阴性对照组(IgG-Fc 9 mg.kg-1)。记录全身评分、关节炎指数、足爪肿胀度、关节肿胀数等整体评价指标、足爪X线摄片、踝关节病理检查及评分,ELISA试剂盒测定腹腔巨噬细胞(PMφ)上清中细胞因子白细胞介素1β(IL-1β),IL-6和肿瘤坏死因子α(TNF-α)水平。结果:RhTNFR:Fc给药组能不同程度地降低AA大鼠升高的全身评分、关节炎指数、足爪肿胀度和关节肿胀数等整体评价指标,减轻AA大鼠的关节炎症,改善AA大鼠X线摄片评分和关节病理学变化,下调PMφ的IL-1β,IL-6和TNF-α的分泌水平。结论:RhTNFR:Fc对大鼠AA的关节炎症具有治疗作用,且抑制腹腔巨噬细胞促炎性细胞因子的表达。

Objective： To investigate the effects of RhTNFR： Fc in an established adjuvant arthritis （AA） rat model and the effects on cytokines production of peritoneal macrophage （PMφ）. Methods： AA was induced by complete Freund adjuvant. AA rats were randomly divided into different groups and then treated with RhTNFR：Fc （1, 3, 9 mg· kg^-1）, or IgG-Fc （9 mg· kg^-1）, respectively after immunization. Arthritis was evaluated by global assessment, polyarthritis index, hind paw swelling, swollen joint count, X-ray of the paws and histopathological examination and histopathological scores. Activities of interleukin-1 β（IL-1β） and interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in supernate of PMφ were assessed by ELISA. Results ： Administration of RhTNFR ： Fc significantly reduced the global assessment score, polyarthritis index, hind paw swelling and swollen joint count, a- meliorated X-ray and histopathological manifestations, and decreased the expressions of IL-1β, IL-6 and TNF-α. Conclusion： Data presented here demonstrate that administration of RhTNFR：Fc significantly attenuates progression of experimental arthritis, and reduces proinflammatory cytokines of PMφ.