高密度脂蛋白改善胶原诱导性关节炎模型小鼠的症状

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (7): 960-964.

高密度脂蛋白改善胶原诱导性关节炎模型小鼠的症状

王昕^1,2, 董庆喆¹, 张娟³, 李冬⁴, 艾迪¹, 王云龙^1,2*

1.青岛大学附属医院生物标本库, 山东青岛 266000;
2.青岛大学药学院, 山东青岛 266021;
3.青岛大学附属医院小儿外科, 山东青岛 266000;
4.青岛大学附属医院泌尿外科, 山东青岛 266000

收稿日期:2020-04-21 修回日期:2020-05-13 出版日期:2020-07-05 发布日期:2020-06-29
通讯作者: ^*wylsun@163.com
基金资助:
山东省重点研发计划(2016GSF201040)

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

WANG Xin^1,2, DONG Qing-zhe¹, ZHANG Juan³, LI Dong⁴, AI Di¹, WANG Yun-long^1,2*

1. Biological Specimen Bank, Affiliated Hospital, Qingdao University, Qingdao 266000;
2. School of Pharmacy, Qingdao University, Qingdao 266021;
3. Department of Pediatric Surgery, Affiliated Hospital, Qingdao University, Qingdao 266000;
4. Department of Urology, Affiliated Hospital, Qingdao University, Qingdao 266000, China

Received:2020-04-21 Revised:2020-05-13 Online:2020-07-05 Published:2020-06-29
Contact: ^*wylsun@163.com

摘要/Abstract

摘要： 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。

关键词: 高密度脂蛋白, 类风湿性关节炎, 肿瘤坏死因子-α, 病理分析

Abstract: 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 type Ⅱ collagen 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 type Ⅱ collagen 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 ofarthritis 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-α and 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.

Key words: high-density lipoprotein, rheumatoid arthritis, tumor necrosis factor-α, pathological analysis

中图分类号:

R392

王昕, 董庆喆, 张娟, 李冬, 艾迪, 王云龙. 高密度脂蛋白改善胶原诱导性关节炎模型小鼠的症状[J]. 基础医学与临床, 2020, 40(7): 960-964.

WANG Xin, DONG Qing-zhe, ZHANG Juan, LI Dong, AI Di, WANG Yun-long. High density lipoprotein improves the symptoms of collagen-induced arthritis in mice[J]. Basic & Clinical Medicine, 2020, 40(7): 960-964.

参考文献

[1] 饶慧玲,王红宁,王凯玲,等.类风湿关节炎患者康复功能锻炼的研究进展[J].护士进修杂志,2019,34:795-798.
[2] 王钰莹,高辉,段京莉.类风湿关节炎免疫治疗药物的作用机制和应用进展[J].临床药物治疗杂志,2019,17:13-17.
[3] Weyand CM,Goronzy JJ.Pathogenesis of rheumatoid arthritis [J].Med Clin North Am,1997,81:29-55.
[4] Rosenson RS,Brewer HB,Ansell B,et al.Translation of high-density lipoprotein function into clinical practice current prospects and future challenges[J].Circulation,2013,128:1256-1267.
[5] Shah AS,Tan L,Long JL,et al.Proteomic diversity of high density lipoproteins:our emerging understanding of its importance in lipid transport and beyond[J].J Lipid Res,2013,54:2575-2585.
[6] Seetharam D,Mineo C,Gormley AK,et al.High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I[J].Circ Res,2006,98:63-72.
[7] EI Harchaoui K,Arsenault BJ,Franssen R,et al.High-density lipoprotein particle size and concentration and coronary risk[J].Ann Int Med,2009,150:84-93.
[8] Moradi H,Streja E,Kashyap ML.et al.Elevated high-density lipoprotein cholesterol and cardiovascular mortality in maintenance hemodialysis patients[J].Nephrol Dialysis Transpl,2014,29:1554-1562.
[9] Vivekanandan-Giri A,Slocum JL,Byun J,et al.High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis[J].Ann Rheumatic Dis,2013,72:1725-1731.
[10] O'Neill F,Charakida M,Topham E,et al.Anti-inflamma-tory treatment improves high-density lipoprotein function in rheumatoid arthritis[J].Heart,2016,103: 766-773.
[11] Kannan K,Ortmann RA,Kimpel D,et al.Animal models of rheumatoid arthritis and their relevance to human disease[J].Pathophysiology,2005,12:167-181.
[12] Toussirot éric,Wendling D.The use of TNF-α blocking agents in rheumatoid arthritis:an update[J].Exp Opin Pharmacother,2007,8:2089-2107.
[13] Guo L,Song ZQ,Li MT,et al.Scavenger receptor BI protects against septic death through its role in modulating inflammatory response[J].J Biol Chem,2009,284:19826-19834.
[14] Cheng AM,Priya H,Sanshiro T,et al.Apolipoprotein A-I attenuates palmitate-mediated NF-κB activation by reduc-ing toll-like receptor-4 recruittment into lipid rafts[J].PLoS One,2012,7.doi:10.1371/journal.pone.0033917.