雌二醇对激素性高眼压大鼠视网膜小胶质细胞和神经节细胞的影响  

Effects of estradiol on retinal microglia and ganglion cells in rats with glucocorticoid-induced ocular hypertension

作　　者：朱宇腾 王松涛[2] 杨华[1] 闫海波 杨瑞[2] 王淑佳 王保君[1] ZHU Yuteng;WANG Songtao;YANG Hua;YAN Haibo;YANG Rui;WANG Shujia;WANG Baojun(Department of Ophthalmology,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,Henan Province,China;Department of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)

机构地区：[1]新乡医学院第一附属医院眼科,河南省新乡市453100 [2]新乡医学院基础医学院,河南省新乡市453003

出　　处：《眼科新进展》2024年第9期697-701,共5页Recent Advances in Ophthalmology

基　　金：新乡市科技攻关计划项目(编号:GG2021030);新乡医学院博士科研基金资助(编号:XYBSKYZZ2015010-505119)。

摘　　要：目的 初步探讨雌二醇对激素性高眼压(OHT)大鼠视网膜中小胶质细胞和视网膜神经节细胞(RGCs)的影响。方法 雄性SD大鼠36只(36眼),随机分为对照组、OHT组和高眼压雌激素处理组(E2-OHT组),每组各12只。其中OHT组和E2-OHT组大鼠在结膜下给予地塞米松磷酸钠注射液,对照组注射相同体积的无菌生理盐水。造模后2周,E2-OHT组大鼠除结膜下注射地塞米松磷酸钠注射液外,同时给予雌二醇滴眼液滴眼。各组大鼠在造模后4周摘取眼球,免疫荧光染色观察大鼠RGCs数量及小胶质细胞活化情况,Western blot检测大鼠视网膜中Brn3a及离子钙结合适配器分子-1(Iba1)蛋白表达,实时荧光定量PCR(RT-PCR)检测大鼠视网膜中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)mRNA的相对表达水平。结果 造模前各组大鼠眼压比较差异无统计学意义(P>0.05)。造模后1周、2周、3周、4周,各组大鼠眼压比较差异均有统计学意义(均为P<0.01)。与对照组相比,造模后1周、2周、3周、4周OHT组大鼠眼压均明显升高,差异均有统计学意义(均为P<0.01)。与OHT组相比,E2-OHT组大鼠造模后1周、2周眼压差异均无统计学意义(均为P>0.05);造模后3周、4周眼压下降,差异均有统计学意义(均为P<0.01)。免疫荧光染色结果显示,对照组大鼠视网膜小胶质细胞主要位于内丛状层,而OHT组大鼠视网膜小胶质细胞迁移到神经节细胞层并且发生了形态学改变(阿米巴样激活状态),E2-OHT组大鼠小胶质细胞形态及分布形式与对照组大鼠视网膜染色结果基本一致。与对照组相比,OHT组大鼠视网膜中RGCs数量减少,TNF-α和IL-1β mRNA相对表达量、Iba1蛋白表达水平均升高,Brn3a蛋白表达水平降低,差异均有统计学意义(均为P<0.05);与OHT组相比,E2-OHT组大鼠视网膜中RGCs数量增多,TNF-α和IL-1β mRNA相对表达量、Iba1蛋白表达水平均降低,Brn3a蛋白表达水平升高,差异均有统计学意�Objective To preliminarily investigate the effects of estradiol on retinal microglia and retinal ganglion cells(RGCs)in rats with glucocorticoid-induced ocular hypertension(OHT).Methods Thirty-six male SD rats(36 eyes)were randomly divided into a control group,an OHT group,and an OHT estradiol-treated group(E2-OHT group),with 12 rats in each group.Among them,the rats in the OHT group and the E2-OHT group were given dexamethasone sodium phosphate injection under the conjunctiva,and the rats in the control group were injected with the same volume of sterile normal saline.Two weeks after modeling,the rats in the E2-OHT group were treated with estradiol eye drops in addition to subconjunctival injection of dexamethasone sodium phosphate.The eyeballs of all rats were removed 4 weeks after modeling.The changes in the number of RGCs and the activation of microglia were observed after immunofluorescence staining,the expression levels of Brn3a and Iba1 proteins in the retina were detected by Western blot,and the relative expression levels of tumor necrosis factorα(TNF-α)and interleukin 1β(IL-1β)mRNA were detected by real-time quantitative polymerase chain reaction.Results Among the three groups,the intraocular pressure(IOP)of rats showed no significant difference before modeling(all P>0.05),but showed a significant difference at 1 week,2 weeks,3 weeks and 4 weeks after modeling(all P<0.01).Compared with the control group,the IOP of rats in the OHT group at 1 week,2 weeks,3 weeks and 4 weeks after modeling increased significantly(all P<0.01).Compared with the OHT group,the IOP of rats in the E2-OHT group showed no significant difference at 1 week and 2 weeks after modeling(both P>0.05),but decreased significantly at 3 weeks and 4 weeks after modeling(both P<0.01).The immunofluorescence staining results showed that the retinal microglia of rats in the control group were mainly concentrated in the inner plexiform layer,while the retinal microglia of rats in the OHT group migrated to the ganglion cell layer and had morpho

关 键 词：糖皮质激素 地塞米松 雌二醇 小胶质细胞 视网膜神经节细胞 

分 类 号：R775.3[医药卫生—眼科]