JAK-STAT信号通路的激活对视网膜缺血-再灌注损伤的促进作用  

Aggravation effects of JAK-STAT signaling pathway in retinal ischemia reperfusion injury

作　　者：杨乐[1] 石蕊[1] 申家泉[2] 薛雨顺[1] 

机构地区：[1]陕西省人民医院眼科,西安710068 [2]山东大学附属省立医院眼科,济南250021

出　　处：《中华实验眼科杂志》2017年第8期690-694,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：陕西省自然科学基金项目（2016JM8121）

摘　　要：背景视网膜缺血-再灌注损伤（RIRI）是眼科临床上常见的多种视网膜血管性疾病共同的病理损伤过程，发病机制复杂。研究表明视网膜细胞凋亡和神经纤维变性是RIRI最终的共同通路。Janus激酶信号转导子与转录激活子（JAK-STAT）信号通路是近年来新发现的一条信号转导途径，参与多种病理生理过程，但该通路与RIRI病理过程的关系尚不明确。目的探讨JAK—STAT信号通路在大鼠RIRI过程中被激活的时程及其意义。方法采用随机数字表法将40只正常清洁级成年SD大鼠随机分为RIRI6h、12h、24h和48h组，大鼠的一侧眼采用前房生理盐水灌注法升高眼压以建立RIRI模型，正常对侧眼作为正常对照组。大鼠眼压升高至110mmHg（1mmHg=0．133kPa）并能持续60min视为造模成功。分别于造模后6、12、24和48h处死大鼠并摘除大鼠眼球，采用免疫组织化学法检测各组大鼠视网膜中STAT3和JAK2蛋白的表达强度并定位；采用实时荧光定量PCR法检测大鼠视网膜中STAT3mRNA和JAK2mRNA相对表达量的动态变化，并与正常对照组检测结果进行比较。结果免疫组织化学检测显示，JAK2和STAT3蛋白主要表达于视网膜内核层和视网膜神经节细胞（RGCs）层，正常对照组大鼠视网膜中JAK2和STAT3蛋白均呈弱阳性表达，呈黄色染色，RIRI模型大鼠视网膜中JAK2和STAT3蛋白表达均明显增强，呈棕黄色染色。各组间大鼠视网膜中JAK2和STAT3蛋白表达强度的总体比较差异均有统计学意义（F=88．735、96．625，均P〈0．01），RIRI后各时间点组大鼠视网膜中JAK2和STAT3蛋白表达强度均明显高于正常对照组，RIRI12h组大鼠视网膜中JAK2和STAT3蛋白表达强度达峰值，均明显高于正常对照组，差异均有统计学意义（JAK2：t=4．308、5．559、5．315、4．726，均P〈0．01；STAT3：t=5．047、7．843、6．281、4．887，均P〈0．01）。RIRI模型眼视网膜内层�Background Retinal ischemia reperfusion injury （RIRI） is a common pathological process oi many retinal vascular diseases with comprehensive pathogenesis mechanism. Researches showed that apoptosis of retinal cells and nerve fiber loss is the finally common pathway of RIRI, and Janus kinase signal transducer and activator of transcription （JAK-STAT） pathway is a newly discovered signal transcript channel in recent years,which is involved in varieties of pathological processes. However,whether JAK-STAT pathway is associated with RIRI is still unelucidated. Objective This study was to investigate the time course of activation of JAK-STAT signal pathway and its significance during RIRI. Methods Forty clear adult male Sprague-Dawley rats were randomized into RIRI 6-hour, 12-hour,24-hour and 48-hour groups. RIRI models were induced in lateral eyes of the rats by perfusing normal saline solution into the anterior chamber to elevate intraocular pressure （lOP） to 110 mmHg for 60 minutes and then allowing reperfusion,and the fellow eyes of the rats served as normal control group. The rats were sacrificed and the eyeballs were enueleated at 6,12,24 and 48 hours after reperfusion. The expressions of JAK2 and STAT3 protein （absorbance） in the retinas were located and detected by immunohistochemistry,and the relative expression levels of JAK2 and STAT3 mRNA in the retinas were detected by real-time fluorescence quantitative PCR. The use and care of the rats followed the ARVO Statement. Results Immunohistochemistry showed that JAK2 and STAT3 were faintly expressed in inner nuclear layer and retinal ganglion cells （RGCs） in the normal control group and strongly expressed in various RIRI groups. Significant differences were found in the expression intensities of JAK2 and STAT3 protein among the five groups （ F = 88. 735,96. 625, both at P 〈 0.01 ）. Compared with the normal control group, the expression intensities of JAK2 and STAT3 were enhanced in RIRI groups,with the peak values in RIRI 12-hour group �

关 键 词：视网膜 缺血-再灌注损伤 信号传导通路 视网膜神经节细胞 Janus激酶信号转导子与 转录激活子 SD大鼠 

分 类 号：R774.1[医药卫生—眼科]