OPG-HSP70对CIA小鼠模型血清学参数的影响及其与疗效的相关性分析  

Effect of OPG-HSP70 on serological parameters of CIA mouse model and its correlation with efficacy

作　　者：夏思思 赵文明[2] 荣雨佳[3] XIA Sisi;ZHAO Wenming;RONG Yujia(Department of Rheumatology and Immunology,Beijing Chao-Yang Hospital,Capital Medical University,Beijing 100020,China;Department of Immunology,School of Basic Medicine,Capital Medical University,Beijing 100069,China;Laboratory Blood Bank,the 731 Hospital Affiliated to China Aerospace Science and Industry Group,Beijing 100074,China)

机构地区：[1]首都医科大学附属北京朝阳医院风湿免疫科,北京100020 [2]首都医科大学基础医学院免疫学系,北京100069 [3]中国航天科工集团七三一医院检验科血库,北京100074

出　　处：《中国医药导报》2019年第31期14-17,共4页China Medical Herald

基　　金：国家自然科学基金资助项目(30873185)

摘　　要：目的探讨骨保护素(OPG)-热休克蛋白70(HSP70)治疗后胶原诱导的关节炎(CIA)小鼠血清学参数变化与病情的相关性。方法将44只雄性DBA/1小鼠分为OPG-HSP70治疗组(n=20)、OPG治疗组(n=12)和模型对照组(n=12);采用尾根部皮内免疫牛Ⅱ型胶原(CⅡ)制备CIA模型,发病后隔日腹腔注射OPG或OPGHSP70融合蛋白,模型对照组注射等量PBS溶液。给药4周后处死小鼠,评估关节炎指数,并经Micro-CT后行骨相对灰度值测算,收集血清检测Ca2+、核因子κB受体活化因子配基(RANKL)、CⅡ抗体,并与关节炎指数和骨密度值进行线性回归分析。结果与模型对照组比较,OPG-HSP70治疗组的关节炎指数明显降低(P <0.01),骨密度值明显增加(P <0.05),CⅡ抗体明显下降(P <0.01),但OPG对炎症和骨破坏的改善不明显。线性回归分析显示,血清Ca2+和RANKL水平与骨密度值呈负相关(r=-0.582、-0.588,均P <0.01);而血清CⅡ抗体水平与关节炎指数呈正相关(r=0.892,P <0.01)。与OPG治疗组比较,给药后1、2、3、4周OPG-HSP70治疗组血清抗OPG抗体明显降低(P <0.01)。结论 OPG-HSP70融合蛋白增加了抗炎症作用,降低了免疫原性,对CIA小鼠的保护作用优于OPG。Objective To investigate the relationship between serum parameters and disease status in collagen-induced arthritis(CIA) mice after OPG-HSP70 treatment. Methods Forty-four male DBA/1 mice were divided into OPG-HSP70 treatment group(n = 20), OPG treatment group(n = 12) and model control group(n = 12). CIA model was induced by intradermal immunization of bovine CⅡ in the tail root. OPG or OPG-HSP70 fusion protein was injected intraperitoneally every other day after arthritis, whereas model control group was injected with the same amount of PBS solution. The mice were sacrificed after 4 weeks of administration, the arthritis index was evaluated, and the relative gray value of bone was measured by Micro-CT. The serum was collected to detect Ca2+, RANKL and type Ⅱ collagen(CⅡ) antibodies. The linear regression was analysis between arthritis index and bone density values and serum data.Results Compared with the model control group, arthritis index of OPG-HSP70 treatment group was significantly reduced(P < 0.01), the BMD value increased obviously(P < 0.05), the CⅡ antibodies lower significantly(P < 0.01).However, OPG did not significantly improve inflammation and bone damage. Linear regression analysis showed that, the serum Ca2 +and RANKL were negatively correlated with the bone density value(r =-0.582,-0.588, all P < 0.01);while the serum CⅡ antibody level was positively correlated with the arthritis index(r = 0.892, P < 0.01). Compared with the OPG treatment group, serum anti-OPG antibodies were significantly lower in the OPG-HSP70 treatment group1, 2, 3, 4 weeks after administration(P < 0.01). Conclusion The OPG-HSP70 fusion protein adds anti-inflammatory effect and reduces immunogenicity, and the protection of CIA mice is better than that of OPG.

关 键 词：骨保护素 热休克蛋白70 胶原诱导的关节炎 滑膜炎 骨破坏 

分 类 号：R392[医药卫生—免疫学]