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脂多糖(LPS)预处理对大鼠内毒素性葡萄膜炎(EIU)的保护作用与白细胞介素-1 受体相关激酶 M(IRAK-M)的过度表达有关。

Protection of Lipopolysaccharide (LPS) Preconditioning against Endotoxin-Induced Uveitis (EIU) in Rats is Associated with Overexpression of Interleukin-1 Receptor-Associated Kinase M (IRAK-M).

机构信息

a Department of Ophthalmology , Beijing Chao-Yang Hospital, Capital Medical University , Beijing , China.

b Department of Ophthalmology , The Third Affiliated Hospital of Chongqing Medical University , Chongqing , China.

出版信息

Ocul Immunol Inflamm. 2018;26(6):943-950. doi: 10.1080/09273948.2017.1291842. Epub 2017 Jun 13.

DOI:10.1080/09273948.2017.1291842
PMID:28609207
Abstract

PURPOSE

To investigate the protective effect of LPS preconditioning against EIU in rats.

METHODS

EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-M Results: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons. The expression of IRAK-1 and IRAK-4 was suppressed in endotoxin tolerance group, whereas IRAK-M was increased.

CONCLUSIONS

Endotoxin tolerance has a protective effect against EIU, and upregulation of IRAK-M through TLR-signaling pathway is one of the most likely candidates to be involved in the observed phenomenon.

摘要

目的

探讨脂多糖预处理对大鼠眼内炎的保护作用。

方法

通过向 Wistar 大鼠皮下注射脂多糖(200μg)建立眼内炎模型。在诱导眼内炎前,每天给予低剂量脂多糖(0.1mg/kg,腹腔内注射)或其载体 5 天。眼内炎诱导 24 小时后,检查眼睛,然后眼球摘出。通过常规组织学检查来确定炎症反应的程度。采用实时 RT-PCR 和 Western blot 检测 NF-kB 的激活以及 IRAK-1、IRAK-4 和 IRAK-M 的表达。

结果

重复给予脂多糖预处理可显著减轻眼内炎症和神经元中 NF-κb p65 的表达。内毒素耐受组 IRAK-1 和 IRAK-4 的表达受到抑制,而 IRAK-M 增加。

结论

内毒素耐受对眼内炎具有保护作用,通过 TLR 信号通路上调 IRAK-M 可能是参与观察到的现象的候选机制之一。

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