胶原诱导关节炎小鼠模型中 HDL 的抗炎作用。

Anti-Inflammatory Effects of HDL in Mice With Rheumatoid Arthritis Induced by Collagen.

机构信息

Biological Specimen Bank, Affiliated Hospital of Qingdao University, Qingdao, China.

Stomatological Department, Qingdao Municipal Hospital, Qingdao, China.

出版信息

Front Immunol. 2018 May 11;9:1013. doi: 10.3389/fimmu.2018.01013. eCollection 2018.

OBJECTIVE

To investigate the anti-inflammatory effects of high-density lipoprotein (HDL) in mice with rheumatoid arthritis (RA) induced by collagen.

METHODS

Male DBA/1 mice (8-week-old) were divided into three groups: control (treated with saline), collagen-induced arthritis (CIA), and CIA + HDL. CIA was induced with bovine type II collagen, and after the injection of bovine type II collagen, the CIA + HDL group received an injection of HDL on day 28 followed by HDL injections four times every 3 days. Mice were weighed, the paws were scored, and paw thickness was measured beginning on day 21. Additionally, the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 were measured by ELISA kits, tissue sections of paws were stained with hematoxylin and eosin, and the inflammatory signaling pathway was analyzed by western blotting.

RESULTS

We found that the production of pro-inflammatory cytokines TNF-α and IL-6 in mice which received HDL decreased 45.14 and 35.02%, respectively. And we also found that HDL could significantly decrease the level of anti-type-II-collagen IgG2a and inhibit the neutrophil infiltration and cell proliferation and protect the ankle joint from type II collage-induced injury. Western blot analysis indicated that HDL could also inhibit the activation of the NF-κB, MAPK, and ERK signaling pathways in RA mice.

CONCLUSION

HDL can inhibit the inflammation induced by bovine type II collagen and the development of RA.

目的

研究高密度脂蛋白（HDL）在胶原诱导的类风湿关节炎（RA）小鼠中的抗炎作用。

方法

雄性 DBA/1 小鼠（8 周龄）分为三组：对照组（生理盐水处理）、胶原诱导关节炎（CIA）组和 CIA+HDL 组。用牛 II 型胶原诱导 CIA，在注射牛 II 型胶原后，CIA+HDL 组在第 28 天接受 HDL 注射，随后每隔 3 天进行 4 次 HDL 注射。从第 21 天开始，对小鼠进行称重、爪子评分和爪子厚度测量。此外，通过 ELISA 试剂盒测量肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平，用苏木精和伊红染色爪子组织切片，并通过 Western blot 分析炎症信号通路。

结果

我们发现接受 HDL 的小鼠中促炎细胞因子 TNF-α和 IL-6 的产生分别降低了 45.14%和 35.02%。并且我们还发现 HDL 可以显著降低抗 II 型胶原 IgG2a 的水平，抑制中性粒细胞浸润、细胞增殖，并保护踝关节免受 II 型胶原诱导的损伤。Western blot 分析表明，HDL 还可以抑制 RA 小鼠中 NF-κB、MAPK 和 ERK 信号通路的激活。