醛糖还原酶基因敲除促进视神经损伤后巨噬细胞向M2方向极化并促进视神经功能恢复

发布时间：2018-01-28 06:01

本文关键词： 醛糖还原酶视神经夹伤视网膜神经节细胞　出处：《细胞与分子免疫学杂志》2014年05期 　论文类型：期刊论文

【摘要】：目的观察小鼠视神经夹伤(ONC)后醛糖还原酶(AR)对视神经损伤后功能恢复的影响及可能机制。方法分别采用C57BL/6-AR+/+(B6野生型)、C57BL/6-AR-/-(AR基因敲除)、Thy1-YFP/AR+/+和Thy1-YFP/AR-/-小鼠,建立ONC模型。行视觉电生理F-VEP检查,观察ONC后AR基因敲除对小鼠视神经转导功能的影响;通过视网膜组织冰冻切片,观察AR基因敲除对Thy1-YFP转基因小鼠ONC后存活视网膜神经节细胞数目的影响;玻璃体内注射Alexa Fluor溲488标记的霍乱毒素B(CTB)顺行标记,观察AR基因敲除对小鼠ONC后神经纤维生长的影响;Western blot法检测野生型小鼠ONC后AR基因的表达变化,及AR基因敲除对M1、M2型巨噬细胞特异性分子诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)表达的影响。结果AR基因敲除可促进小鼠ONC后视神经转导功能的恢复,增加存活的视神经节细胞数量;AR基因敲除可促进小鼠ONC后视神经纤维生长;AR基因敲除可促使小鼠ONC后巨噬细胞向M2方向极化。结论 AR可能通过调节视神经损伤后巨噬细胞极化影响视神经功能恢复。
[Abstract]:Objective To observe the effects of optic nerve crush injury in mice (ONC) after aldose reductase (AR) recovery of function after optic nerve injury and its possible mechanism. Methods C57BL/6-AR+/+ (B6 wild type), C57BL/6-AR-/- (AR knockout), Thy1-YFP/AR+/+ and Thy1-YFP/AR-/- mice to establish ONC model. For visual electrophysiological examination of F-VEP, ONC after the effects of AR gene knockout on mouse optic nerve transduction; by retinal tissue sections to observe the effects of AR gene knockout on the survival of retinal ganglion cell number of Thy1-YFP transgenic mice after ONC; cholera toxin B glass in vivo injection of Alexa labeled Fluor form 488 (CTB) anterograde labeling, to observe the effects of AR gene knockout on the growth of nerve fibers in mice after ONC; expression of gene in wild-type mice after ONC AR Western blot, and AR gene knockout on M1 and M2 macrophages induced a specific molecular oxygen NO synthase (iNOS), arginase 1 (Arg1) on the expression of the AR gene knockout. ONC can promote the recovery of optic nerve transduction function of mice, increase the number of surviving retinal ganglion cell; AR gene knockout can promote optic nerve fibers in mice ONC growth; AR gene knockout mice can promote ONC after the M2 macrophage polarization. Conclusion AR may regulate nerve injury after macrophage polarization optic nerve function recovery.

【作者单位】：第四军医大学西京医院全军眼科研究所;第四军医大学神经生物学教研室;
【基金】：陕西省自然科学基础研究计划重点项目(2012J24002)
【分类号】：R779.1
【正文快照】： 醛糖还原酶(aldose reductase,AR)属于醛酮还原酶超家族,人类AR主要由AKR1B1编码,染色体定位在7q35上,由315个氨基酸组成,相对分子质量(Mr)约36 000,AR是多元醇通路中重要的限速酶,催化还原型烟酰胺腺嘌呤二核苷酸磷酸(reducednicotinamide adenine dinucleotide phosphate,NA

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