重组人白细胞介素-1受体拮抗剂对大鼠胶原性关节炎的治疗作用

Therapeutic effects of recombinant human interleukin 1 receptor antagonist on type Ⅱ collagen-induced arthritis rats

目的 研究重组人白细胞介素 1受体拮抗剂 (recom binanthumaninterleukin1receptorantagonist, rhIL 1ra)对大鼠胶原性关节炎 (collagen inducedarthritis,CIA)的治疗作用。方法 SD大鼠随机分为 6组:正常对照组、模型组、rhIL 1ra3个剂量组和进口IL 1ra组;采用Ⅱ型胶原(CⅡ)乳剂皮内注射诱导大鼠CIA模型;每周测体重观察体重变化;足爪容积法测量大鼠足爪肿胀度;测定CⅡ的迟发性变态反应(DTH);ELISA法检测血清中抗Ⅱ型胶原抗体水平;同时进行病理组织学的检查。结果 CIA大鼠在致炎d10,出现关节红、肿,体重减轻,血清抗CⅡ抗体水平升高,关节病理可见滑膜增生,炎性细胞浸润,血管翳形成,软骨和骨的破坏等。rhIL 1ra(7 5, 30, 120mg·kg-1 )和阳性对照组anakinra(120mg·kg-1 )皮下注射,连续 7d,能明显抑制CIA大鼠足肿胀;rhIL 1ra(30, 120mg·kg-1 )皮下注射,连续 7d,可以明显减轻CⅡ诱发的迟发性变态反应 (DTH);另外,rhIL 1ra也可明显降低CIA大鼠血清中抗CⅡ抗体的水平;病理学检查表明,rhIL 1ra大剂量能明显减轻CIA大鼠关节滑膜炎症和滑膜增生,减轻血管翳和软骨破坏。结论 rhIL 1ra对CIA具有治疗作用。

Aim To study the therapeutic effects of recombinant huma n interleukin 1 receptor antagonist (rhIL-1ra) on type Ⅱ collagen-induced arthr itis(CIA) rats. Methods SD rats were divided randomly into six groups including normal, model, rhIL-1ra(7.5,30,120 mg·kg -1) and anakinra( 120 mg·kg -1) groups. Collagen Ⅱ emulsion was used to induce CIA model i n rats. The body weight was observed once a week. Paw swelling of CIA rats was m easured with volume meter. CⅡ induced delayed-type hypersensitivity(DTH) was m easured. Meanwhile, the level of anti-CⅡIgG antibody in serum was assayed by E LISA. Results The onset of paw swelling was on d10 after injection o f emulsion. The level of serum anti-CⅡIgG antibody was increased significantly in CIA. Pathological changes in joints of CIA rats showed hyperplastic synoviu m of CIA, inflammatory cells infiltration, pannus, destruction of cartilage and bone. rhIL-1ra(7.5,30,120 mg·kg -1·d -1×7 d) and anakinra(120 mg·kg -1·d -1×7 d) subcutaneous injection(sc) inhibited inflammat ory swelling. rhIL-1ra(30,120 mg·kg -1·d -1×7 d) significantly s uppressed the DTH reaction induced with CⅡ in CIA rats. Moreover,rhIL-1ra red uced the level of anti-CⅡ IgG antibody in serum. Pathological examination show ed rhIL-1ra(120 mg·kg -1·d -1×7 d) significantly improved subcho ndral inflammation, synovium hyperplasia, pannus and cartilage damage. Con clusion rhIL-1ra has therapeutic effects on CIA rats.