重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白关节腔注射对胶原诱导性关节炎大鼠骨及软骨代谢的影响  

Influence of recombinant human soluble tumor necrosis factor receptor Ⅱ: IgG Fc fusion protein articular injection on bone and cartilage metabolism of collagen-induced arthritis rats

作　　者：黄志祥[1] 邓伟明[1] 郭欣[1] 黄学婵 李天旺[1] HUANG Zhi-xiang;DENG Wei-ming;GUO Xin(Department of Rheumatology and Immunology,Guangdong Second Provincial General Hospital,Guangzhou Guangdong 510317,China)

机构地区：[1]广东省第二人民医院风湿免疫科,广东广州510317

出　　处：《临床和实验医学杂志》2019年第2期137-139,共3页Journal of Clinical and Experimental Medicine

基　　金：广东省医学科研基金项目(编号:2015517)

摘　　要：目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(Rh TNFR:Fc)关节腔注射对胶原诱导性关节炎(CIA)大鼠疾病活动性、软骨及骨代谢的影响。方法将30只CIA大鼠随机分为3组,给予每周1次共4次右踝关节注射。Ⅰ组大鼠首次注射Rh TNFR:Fc,随后三次注射生理盐水,Ⅱ组及Ⅲ组大鼠则分别注射4次Rh TNFR:Fc或生理盐水。在基线期及每次治疗1周后(分别定义为随访1、2、3及4)通过测量右足体积评估病情。完成随访4后检测血清核因子κB受体活化因子配体(RANKL)、骨保护素(OPG)、Ⅱ型胶原C端肽(CTX-Ⅱ)及软骨寡聚基质蛋白(COMP)的水平,分离右踝关节以Mankin评分评价软骨病理改变。结果Ⅰ组大鼠随访1时右足体积显著下降(P <0. 05),之后逐渐回升。Ⅱ组大鼠各随访期右足体积逐渐下降,而Ⅲ组大鼠右足体积逐渐上升。完成随访4后Ⅰ组大鼠血清RANKL、RANKL/OPG值、CTX-Ⅱ、COMP及右踝关节Mankin评分显著高于Ⅱ组大鼠(P <0. 05),但明显低于Ⅲ组大鼠(P <0. 05)。血清OPG趋势与之相反。结论关节腔注射RhTNFR:Fc在缓解大鼠CIA病情的同时,改善骨及软骨代谢。Objective To investigate the effect of recombinant human soluble tumor necrosis factor receptor Ⅱ:IgG Fc fusion protein(RhTNFR:Fc)articular injection on disease activity,bone and cartilage metabolism of rats with collagen-induced arthritis(CIA).Methods 30 CIA rats were randomized into 3 groups.Group Ⅰ received normal saline thrice after RhTNFR:Fc local injection on right ankle,while Group Ⅱ and Ⅲ undertook 4 times RhTNFR:Fc or normal saline local injection respectively.Right paw volume was assessed by plethysmometry at baseline and every week after treatment(visit 1,2,3,and 4).Serum receptor activator for nuclear factor-κB ligand(RANKL),osteoprotegerin(OPG),C-telopeptide of typeⅡcollagen(CTX-Ⅱ)and cartilage oligomeric matrix protein(COMP)were measured after the final visit.Mankin score was employed to evaluate histological change of cartilage in right ankles.Results Right paw volume of GroupⅠat first visit was significantly lower than that of baseline(P<0.05),but elevated during following visits.Additionally,right paw volume gradually dropped at each visit in GroupⅡbut kept increasing in GroupⅢ.Serum RANKL,RANKL/OPG,CTX-Ⅱ,COMP and Mankin score of Group I were significantly higher than those of Group II,but lower than in Group III.The trend of OPG was opposite.Conclusion RhTNFR:Fc articular injection ameliorates disease activity of CIA,and improves bone and cartilage metabolism.

关 键 词：大鼠 胶原诱导性关节炎 关节腔注射 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白 骨代谢软骨代谢 

分 类 号：R593.2[医药卫生—内科学]