重组人Ⅱ型肿瘤坏死因子受体一抗体融合蛋白局部注射治疗胶原诱导性关节炎大鼠的疗效观察  

Efficacy of local injection of RhTNFR：Fc in collagen-induced arthritis of rats

作　　者：王敏[1] 黄志祥[2] 谭锦辉[1] 邓伟明[2] 李天旺[2] 

机构地区：[1]中山大学附属第三医院风湿科,广州510630 [2]广东省第二人民医院风湿免疫科

出　　处：《中华医学杂志》2013年第37期2989-2992,共4页National Medical Journal of China

基　　金：广东省科技计划项目（20098080701034）

摘　　要：目的 观察局部注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（RhTNFR：Fc）对胶原诱导性关节炎（CIA）大鼠的疗效.方法 将24只CIA大鼠随机分为单次治疗组（Ⅰ组）、多次治疗组（Ⅱ组）及空白对照组（Ⅲ组）.所有大鼠均选取病变较重的右踝关节进行局部注射,每周1次共4次.Ⅰ组大鼠首次注射RhTNFR：Fc,随后3次注射生理盐水,Ⅱ组及Ⅲ组大鼠则分别注射4次RhTNFR：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）均采用关节炎指数（AI）评价大鼠右踝关节及全身炎症的活动状况.完成随访4后检测大鼠血清C反应蛋白（CRP）浓度,并分离右踝关节行X线及病理学检查.结果 Ⅰ组随访1时局部及全身AI较基线期明显降低（P＜0.05）,但随后逐渐回升.Ⅱ组各随访期局部及全身AI均逐渐下降,而Ⅲ组上述指标无下降趋势.Ⅰ、Ⅱ组放射学评分分别为（5.70±0.67）分及（4.90±0.73）分,病理学评分分别为（6.00±0.67）分及（3.80±0.91）分,血清CRP浓度分别为（7.50±0.87） μg/ml及（3.09±0.76） μg/ml,明显低于Ⅲ组的（6.60±1.26）分、（7.10±0.74）分及（12.15 ±3.47） μg/ml（P ＜0.05）,且Ⅰ组显著高于Ⅱ组（P＜0.05）.结论 RhTNFR：Fc单次及多次局部注射均能有效缓解CIA病情,降低CRP浓度、放射学及病理学评分.单次注射病情易反复,疗效不及多次注射.Objective To evaluate the efficacy of recombinant human tumor necrosis factor-αreceptor Ⅱ：IgG fusion protein （RhTNFR：Fc） local injection in collagen-induced arthritis （CIA） of rats.Methods Twenty-four CIA rats were randomly divided into 3 groups：single therapy （Group Ⅰ）,multiply therapies （Group Ⅱ） and control （Group Ⅲ）.Group Ⅰ received normal saline thrice after a single RhTNFR：Fc local treatment while Groups Ⅱ and Ⅲ had 4 times of RhTNFR：Fc or normal saline local injection.The severities of right ankle and systemic inflammation were assessed by arthritis index （AI） at baseline and every week after local injection （visits 1,2,3 and 4）.Serum C reactive protein （CRP） was measured after the last visit.And right ankles were further examined through radiology and pathology.Results Local or systemic AI of Group Ⅰ were significantly lower than that of baseline at visit 1 （P 〈 0.05）,but increased during other visits.And local or systemic AI of Group Ⅱ gradually decreased at each follow-up,but AI of Group Ⅲ showed no decline.The radiographic scores （5.70 ± 0.67 and 4.90 ± 0.73）,histopathological scores （6.00 ± 0.67 and 3.80 ± 0.91） and serum CRP concentration （7.50 ± 0.87 and 3.09 ± 0.76 μg/ml） of Group Ⅰ and Group Ⅱ were lower than those of Group Ⅲ （6.60 ± 1.26,7.10 ± 0.7 and 12.15 ±3.47 μg/ml,P 〈0.05）.And all these parameters of Grouplwere higher than those of Group Ⅱ （P 〈 0.05）.Conclusion Local injection of RhTNFR：Fc can effectively alleviate disease activity of CIA and reduce CRP concentration,radiographic and histopathological scores.Multiple therapies show a better efficacy than single injection.

关 键 词：重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白 踝关节 关节内注射 胶原诱导 性关节炎 

分 类 号：R593.22[医药卫生—内科学]