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

发布时间：2018-05-01 18:02

本文选题：视网膜色素上皮细胞 + 光损伤　；参考：《眼科新进展》2014年10期

【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(P0.01)。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(P0.01)。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P0.05)。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P0.05);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P0.05)。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。
[Abstract]:Objective to study the expression of metalloproteinase-tissue inhibitor of metalloproteinase-1 (TIMP-1) and extracellular signal-regulated protein kinase 1(extracellular regulated protein kinase-1 (ERK-1) in pigment epithelium of retinal pigment epithelial cells (RPE) and the effect of erythropoietin (EPO) on the expression of metalloproteinase-1 and extracellular signal-regulated protein kinase 1(extracellular regulated protein kinase-1ERK-1 in experimental light injured mouse retinal pigment epithelial cells (RPE), and to investigate the effects of erythropoietin on the expression of metalloproteinase-1 and extracellular signal-regulated protein kinase (1(extracellular regulated). To investigate the protective mechanism of EPO on retinal light injury. Methods the animal model of retinal light injury in rats was established. Recombinant human erythropoietin human was injected intraperitoneally into mice before illumination. Morphological changes of RPE cells were observed by HE staining and the expression of TIMP-1 ERK-1 protein was detected by immunohistochemistry. Results Light injury could cause progressive damage of RPE cells in mouse retina. Exogenous EPO can increase the expression of TIMP-1 and ERK-1 in retinal RPE cells after light injury. The density of RPE cells decreased gradually with the prolongation of illumination time, and the density of RPE cells was significantly different from that of the normal control group 7 days after irradiation (P 0.01). The density of RPE cells in the group treated with EPO at the same time after light exposure was slightly higher than that in the control group, and there was a significant difference between the two groups on the 7th day after light exposure (P 0.01). The expression of ERK-1 in EPO treatment group was significantly higher than that in light group (P 0.05). There was no significant difference in the expression of TIMP-1 between the light group and the EPO treatment group at 6 h and 7 d after illumination (P0.05), and the expression of TIMP-1 in the EPO treatment group was higher than that in the simple illumination group at every time point from 12 h after illumination to 96 h after illumination (all the results showed that the expression of TIMP-1 in the treated group was significantly higher than that in the control group (P < 0.05). There was a positive correlation between the expression of TIMP-1 and the expression of ERK-1 in P0.05).EPO treated group. Conclusion exogenous EPO can increase the expression of TIMP-1 in retinal RPE cells after light injury, which is beneficial to the restoration of MMPs/TIMP balance. It is further confirmed that the protective effect of EPO on retinal light injury. The regulation of TIMP-1 secretion and expression in RPE cells may be via MAPK pathway.
【作者单位】：烟台市经济技术开发区医院眼科;青岛大学医学院附属医院眼科;
【基金】：国家自然科学基金资助(No:30572010)~~
【分类号】：R774.1

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