高密度脂蛋白改善胶原诱导性关节炎模型小鼠的症状

High density lipoprotein improves the symptoms of collagen-induced arthritis in mice

目的探讨高密度脂蛋白(HDL)对胶原诱导性关节炎(CIA)小鼠的作用。方法将小鼠随机分为对照组、CIA组、CIA+HDL组。应用Ⅱ型胶原蛋白诱导建立关节炎小鼠模型,尾静脉注射高密度脂蛋白(10 mg/kg),每3 d注射1次,共注射5次。期间记录小鼠体质量变化和关节炎临床评分。第75天处死小鼠,使用ELISA试剂盒测定小鼠血清中肿瘤坏死因子-α(TNF-α)、Ⅱ型胶原特异性抗体IgG2α的水平,将小鼠踝关节组织切片用HE染色,分析各组小鼠类风湿性关节炎的严重程度以评价高密度脂蛋白对于类风湿性关节炎的作用。结果与CIA组相比,静脉注射10 mg/kg的HDL可以显著改善小鼠类风湿性关节炎的症状。实验结果显示HDL可以减轻关节炎临床症状,降低血清中促炎因子TNF-α以及特异性抗体IgG2α表达水平(P<0.05)。病理组织学检测显示HDL可以使小鼠踝关节关节面变光滑,明显改善滑膜增生、炎性细胞浸润与骨侵蚀等病理变化。结论HDL对类风湿性关节炎小鼠的症状有显著的改善作用。

Objective To investigate the effects of high-density lipoprotein(HDL)on collagen-induced arthritis(CIA)animal model.Methods DBA/1 mice were divided into three groups:control group,CIA group and CIA+HDL group.Mice in the CIA and CIA+HDL groups were immunized with an emulsion of Freund's complete adjuvant and bovine typeⅡcollagen on day 0.The control group was injected with saline.On day 21,the CIA group and CIA+HDL group were injected with an emulsion of Freund's incomplete adjuvant and bovine typeⅡcollagen to streng then the immune response.The control group was injected with saline only.The CIA+HDL group was injected with HDL(10 mg/kg)on day 40 followed by HDL injection five times every 3 days.The control group and the CIA group were injected with the same volume of saline.Changes in mouse body weight and clinical scores of arthritis were recor-ded.The mice were sacrificed on day 75,and the serum levels of tumor necrosis factor-α,anti-collagen-Ⅱ antibody IgG2a of the mice were measured using ELISA kit.Then the tissue sections of ankle joints were stained with hematoxylin-eosin to analyze the severity of rheumatoid arthritis in mice to evaluate the efficacy of high-density lipoprotein in the treatment of rheumatoid arthritis.Results Compared with the CIA group,intravenous injection of HDL at a dose of 10 mg/kg significantly alleviated the symptoms of rheumatoid arthritis in mice.The results showed that HDL alleviated the clinical symptom of arthritis and decreased the level of serum pro-inflammatory factor TNF-αand specific antibody of IgG2α(P<0.05).Histopathological examination showed that HDL can smoothen the ankle articular surface,significantly decrease synovial hyperplasia,inflammatory cell and bone erosion and other pathological changes.Conclusions HDL can significantly alleviated the symptoms of collagen-induced rheumatoid arthritis of mice.