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合成糖皮质激素诱导亮氨酸拉链肽抑制脂多糖诱导的大鼠眼内炎症。

Synthetic Glucocorticoid-Induced Leucine Zipper Peptide Inhibits Lipopolysaccharide-Induced Ocular Inflammation in Rats.

机构信息

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China,

出版信息

Ophthalmic Res. 2020;63(4):434-442. doi: 10.1159/000505003. Epub 2019 Nov 26.

Abstract

PURPOSE

To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats.

METHODS

The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection.

RESULTS

Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1β, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p.

CONCLUSION

The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease.

摘要

目的

在大鼠内毒素性葡萄膜炎(EIU)模型中,展示一种合成的糖皮质激素诱导亮氨酸拉链(GILZ98-134)肽(GILZ-p)的抗炎作用。

方法

通过玻璃体内注射脂多糖(LPS)在 Sprague Dawley 大鼠中诱导 EIU 模型。在 LPS 注射后 6 小时,玻璃体内注射合成的 GILZ-p。为了评估 GILZ-p 的抗炎作用,在 GILZ-p 注射后第 0、1、2、3 和 4 天,通过裂隙灯显微镜评估大鼠眼前房和虹膜的炎症反应。在 GILZ-p 注射后第 0、1、2、3 和 4 天,测量视网膜中炎症细胞因子的表达。在 GILZ-p 注射后的预定时间点,还检测了 Müller 细胞胶质增生。

结果

在 EIU 模型中,LPS 注射后 24 小时前节炎症达到高峰。与对照组相比,玻璃体内 GILZ-p 显著抑制了 EIU 大鼠的 LPS 诱导的前节炎症。玻璃体内 GILZ-p 注射同时降低了视网膜炎症因子 IL-1β、TNF-α、MCP-1 和 ICAM-1 的水平。EIU 视网膜中的波形蛋白表达显著减少,GILZ-p 显著恢复了 EIU 视网膜中下调的水通道蛋白 4。

结论

合成的 GILZ-p 抑制了 EIU 模型中的炎症反应,可能对治疗炎症性眼病有一定的应用价值。

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