视网膜光损伤中TIMP-1、ERK-1的表达及促红细胞生成素对其影响  

Expression of TIMP-1 and ERK-1 in retinal light-induced injury and effects of EPO on it

作　　者：王颖立 牛膺筠[2] 

机构地区：[1]烟台市经济技术开发区医院眼科,山东省烟台市264006 [2]青岛大学医学院附属医院眼科,山东省青岛市266003

出　　处：《眼科新进展》2014年第10期911-914,共4页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(No:30572010)~~

摘　　要：目的研究实验性光损伤小鼠视网膜色素上皮细胞(retinal pigment epithelium,RPE)中金属蛋白酶组织抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)及细胞外信号调节蛋白激酶1(extracellular regulated proteinkinase-1,ERK-1)表达的变化,以及促红细胞生成素(erythropoietin,EPO)对其的影响,探讨EPO对视网膜光损伤发挥保护作用的机制。方法建立大鼠视网膜光损伤动物模型,于小鼠光照前腹腔注射重组人促红细胞生成素(recombination human erythropoietin,rhEPO),采用HE染色观察RPE细胞形态学变化,免疫组织化学法检测其TIMP-1、ERK-1蛋白的表达。结果光损伤可以造成小鼠视网膜RPE细胞渐进性的破坏。外源性的EPO可以促进光损伤后视网膜RPE细胞TIMP-1及ERK-1表达的增加。随光照时间延长,单纯光照组RPE细胞密度逐渐减少,光照后7 d RPE细胞密度与正常对照组比较差异有统计学意义(P<0.01)。光照后相同时间点,EPO处理组的RPE细胞密度较单纯光照组稍有增加,光照后7 d二者差异有统计学意义(P<0.01)。光照后各时间点,EPO处理组均较单纯光照组中ERK-1的表达明显增强(均为P<0.05)。光照后6 h、7 d,单纯光照组和EPO处理组中TIMP-1的表达差异均无统计学意义(均为P>0.05);自光照后12 h起至光照后96 h,各时间点EPO处理组较单纯光照组中TIMP-1的表达增强(均为P<0.05)。EPO处理组RPE中TIMP-1的表达与ERK-1的表达正相关(r=0.79,P=0.03)。结论外源性EPO通过增加光损伤后视网膜RPE细胞TIMP-1的表达,有利于MMPs/TIMP平衡的恢复,进一步证实EPO对视网膜光损伤的保护作用。EPO对RPE细胞TIMP-1分泌和表达的调节可能经由MAPK途径。Objective To study the changes of expression of tissue inhibitor of metalloproteinase-1（ TIMP-1） and extracellular regulated proteinkinase-1（ ERK-1） in light-induced retinal pigment epithelium（RPE） degeneration,and the effects of erythropoietin（EPO） on it,in order to investigate the possible mechanism of EPO protective function. Methods On the basis of establishment of mouse retinal light injury animal models,the recombination human erythropoietin（rhEPO） was injected into the abdominal cavity before illumination. Morphology difference of RPE was examined by HE staining. The expressions of TIMP-1,ERK-1 were examined by immunohistochemical method. Results Continuous light exposure could cause general RPE degeneration in mice. Exogenous EPO could increase TIMP-1 and ERK-1 expression in RPE after irradiation. The RPE cell density was decreased in simple irradiation group,there was significant difference at 7 days compared with normal control group（ P 0. 01）. The RPE cell density in EPO treated group was higher slightly than simple irradiation group,there was significant difference at7 days between two groups（P 0. 01）. The ERK-1 expression in EPO treated group were higher than simple irradiation group at all time points（all P 0. 05）. There was no statistical difference in TIMP-1 expression at 6 hours and 7 days after irradiation between simple irradiation group and EPO treated group（all P 0. 05）. The expression of TIMP-1 in EPO treated group were higher than those in simple irradiation group from 12 hours to 96 hours after irradiation（all P 0. 05）.TIMP-1 expression was positive linear associated with ERK-1 expression in EPO treated group（r =0.79,P =0. 03）. Conclusion Exogenous EPO can increase TIMP-1 expression in RPE cell after light exposure,and then be beneficial to regain the balance between MMP and TIMP,so the protective function of EPO for light-induced retinal degeneration is further confirmed. In addition,EPO may regulate the secretion and expression of TIMP-1 in RPE

关 键 词：视网膜色素上皮细胞 光损伤 促红细胞生成素 金属蛋白酶组织抑制物-1 细胞外信号调节激酶蛋白1 

分 类 号：R692.5[医药卫生—泌尿科学]