载地塞米松纳米胶束治疗类风湿性关节炎的体内药效学研究

In vivo pharmacodynamics ofγ-PGA-DEX micelles in the treatment of rheumatoid arthritis

目的研究以γ-聚谷氨酸(γ-PGA)载体包载地塞米松(DEX)制备的γ-PGA-DEX纳米胶束治疗类风湿关节炎的体内药效学。方法采用DBA/1小鼠建立胶原蛋白诱导的关节炎(collagen-induced arthritis,CIA)模型,于首次免疫后第21 d,按关节炎评分,随机将小鼠分组,每组5只,通过尾静脉注射γ-PGA-DEX;按各组给药剂量每3 d给药。每次给药过程中对小鼠关节肿胀度、体重变化、关节评分,并对小鼠踝关节进行组织病理学检查。除此之外,采用ebiosicence的小鼠TNF-α、IL-1β和IL-6测定试剂盒进行测定小鼠血清中的前炎症因子TNF-α、IL-1β和IL-6。结果与空白组小鼠相比,治疗期间γ-PGA-DEX组小鼠体重呈现增长趋势,关节指数评分显著低于游离DEX治疗组,且在所有治疗组中最低,显示出其较好的治疗效果;关节病理切片HE染色显示,γ-PGA-DEX组与normal组相比没有显著性差异,无明显的炎性细胞浸润和骨破坏现象,病理评分为2分。相较于游离组,γ-PGA-DEX组小鼠血清中TNF-α、IL-1β、IL-6炎性因子的含量均显著降低(P<0.01)。结论γ-PGA-DEX具有较好的治疗类风湿关节炎的效果,是一种具有潜在应用前景的治疗类风湿关节炎及其它炎症疾病的纳米药物。

ObjectiveTo investigate the in vivo pharmacodynamics ofγ-PGA-DEX micelle which was prepared by loading dexamethasone(DEX)withγ-polyglutamic acid(γ-PGA)in the treatment of rheumatoid arthritis(RA).MethodsDBA/1 mice were used to establish the collagen-induced arthritis(CIA)model.On the 21st day after the first immunization,the mice were randomly grouped according to the arthritis scores,with 5 mice in each group,andγ-PGA-DEX was given by tail vein injection every 3 days according to the dose of each group.The joint swelling degree,weight change,joint score and histopathological examination of ankle joint were performed during each administration.In addition,the ebiosicence mouse TNF-α,IL-1βand IL-6 kits were used to determine the pro-inflammatory cytokines TNF-α,IL-1βand IL-6 in mouse serum.ResultsCompared with the blank group,the body weight of mice in theγ-PGA-DEX group showed an increasing trend during the treatment,and the joint index score was significantly lower than that of the free DEX treatment group,and it was the lowest in all treatment groups,showing a good therapeutic effect.HE staining of joint pathological sections demonstrated that there was no significant difference between theγ-PGA-DEX group and the normal group.Furthermore,there was no obvious inflammatory cell infiltration and bone destruction,and the pathological score was 2.Compared with the free group,the levels of TNF-α,IL-1βand IL-6 in the serum of mice in theγ-PGA-DEX group were significantly decreased(P<0.01).Conclusionγ-PGA-DEX micelle showed good therapy effect in the treatment of RA,and it would be a nano-drug with potential application prospect in the treatment of rheumatoid arthritis and other inflammatory diseases.