雌激素受体GPR30介导的小鼠视网膜神经节细胞保护作用  

Neuroprotection of Estrogen Receptor GPR30 in Retinal Ganglion Cell

作　　者：江梦南 罗雪[1] 沈雨濛 刘诗亮[1] 娄翔峰 胡单萍 沈吟[1] 邢怡桥[1] 

机构地区：[1]武汉大学人民医院眼科中心,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2016年第2期195-199,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金面上项目(编号:81270998;81470628;81271025)

摘　　要：目的:通过玻璃体腔注射N-甲基-D-天冬氨酸(NMDA)建立小鼠青光眼模型,研究G蛋白偶联受体30(GPR30)对受损的视网膜神经节细胞的保护作用。方法:选取7-9周龄C57雄性小鼠,利用荧光染色技术,观察GPR30受体在正常雄鼠视网膜内分布。将健康雄鼠随机分为4组:1对照组;2NMDA模型组;3GPR30受体激动剂(G-1)组;4雌激素和GPR30受体拮抗剂(G-15)组。通过全视网膜铺片Brn3a免疫荧光染色、视网膜冰冻切片免疫荧光染色和神经节细胞计数,观察玻璃体腔注射NMDA后各组小鼠视网膜神经节细胞和视网膜胶质细胞的变化。结果:在正常雄鼠视网膜中,GPR30受体主要表达在内核层和神经节细胞层。光镜下观察雌激素组和G-1组中Brn3a特异性标记的神经节细胞较NMDA模型组神经节细胞密度增高,GFAP标记的胶质细胞较NMDA模型组则明显减少;神经节细胞计数显示:雌激素组和GPR30受体激动剂(G-1)组均较NMDA模型组神经节细胞数量明显增高(P<0.05)。结论:雌激素主要通过激活GPR30受体保护视网膜神经节细胞,在NMDA损伤的视网膜神经节细胞模型中,GPR30受体的激活可减少视网膜胶质细胞的增生。Objective： To investigate the neuroprotection of G protein-coupled receptor 30 （GPR30/ GPER-1） in retinal ganglion cells （RGCs） which were induced by N-methyl-D-aspartate （NM- DA）. Methods： Healthy C57BL/6J mice of 7-9 weeks old were randomly divided into 4 groups： control; NMDA; GPR30 agonist （G-1）; Estrogen and G-15. Immunofluorescence staining by GPR30 was taken to study the expression pattern of GPR30 in normal mouse retina. The retina with NMDA was marked by Brn3a to count the number of retinal ganglion cells. Glial fibrillary acidic protein （GFAP） was taken to study the Mtiller cells in the neuroprotection of reti- na by 17β-estrogen and GPR30. Results： GPR30 represented on retinal ganglion cells layer （RGCL） and inner nuclear layer （INL）. Cell counting revealed a significant recovery of RGCs in NMDA model mice with estrogen and GPR30 agonist （G-l） （P〈0.05）. There was also a prolif- eration inhibition of Muller cells in NMDA model mice with estrogen and G-1. Conclusion： The RGCs can be mainly protected by activating estrogen receptor GPR30, which can inhibit the pro- liferation of Mailer cells.

关 键 词：雌激素 G蛋白偶联受体30 视网膜神经节细胞 N-甲基-D-天冬氨酸 

分 类 号：R774.1[医药卫生—眼科]