信号转导/转录激活因子3抗ARPE-19细胞氧化应激研究  

Protective effects of STAT3 on retinal pigmented epithelium cells against oxidative stress

作　　者：李兰根 伟伟 张玉凤 格日乐图 

机构地区：[1]内蒙古自治区人民医院眼科,内蒙古自治区呼和浩特市010017

出　　处：《眼科新进展》2016年第11期1020-1023,共4页Recent Advances in Ophthalmology

基　　金：内蒙古自治区自然科学基金资助项目(编号:2016MS0872)~~

摘　　要：目的本研究旨在观察信号转导/转录激活因子3(signal transduction/activation of transcription factor3,STAT3)对视网膜色素上皮细胞(retinal pigment epithelium cells,RPE)氧化应激损伤的保护作用,并探讨STAT3在年龄相关性黄斑变性(age-related macular degeneration,AMD)发病机制中的意义。方法体外培养ARPE-19细胞系,氧化低密度脂蛋白及H2O2干预培养细胞诱导氧化应激损伤,通过对细胞增殖、凋亡、活性氧族(reactive oxygen species,ROS)水平及细胞衰老分析研究,评估氧化应激损伤对RPE的影响;实时荧光定量技术分析氧化应激过程中STAT3-mRNA表达状况;STAT3过表达载体转染ARPE-19细胞,烟酰胺预处理细胞再经H2O2及氧化低密度脂蛋白干预后通过对增殖、凋亡、ROS及细胞衰老状态的分析,了解STAT3抗RPE氧化应激效果。结果与对照组相比,H2O2和氧化低密度脂蛋白能显著增加ROS水平,促使细胞衰老增加,细胞的增殖显著下降而细胞凋亡显著上升(均为P<0.05)。氧化应激状况下STAT3上游产物表达上升,氧化低密度脂蛋白及H2O2组荧光表达强度分别是3.3±1.2及3.5±1.1,与对照组相比差异均有统计学意义(均为P<0.05);STAT3能保护ARPE-19细胞抗氧化应激损伤,使细胞增殖增加、凋亡减少及ROS累积,但不造成细胞衰老状况加剧,说明ARPE-19细胞衰老不受STAT3调节。结论STAT3在细胞氧化损伤中能独立地发挥抗氧化应激作用,提示了STAT3在AMD治疗过程中的应用前景。Objective To observe the protective effects of signal transduction/ activation of transcription factor 3 （ STAT3 ） on retinal pigment epithelial （RPE） cells against oxidative stress, and explore its role in the pathogenesis of age-related macular degeneration （AMD）. Methods APRE-19 cell lines were cultured in v/tro and the oxidative stress injury was induced by oxidized low density lipoprotein （ox-LDL） and H2O2. The rates of proliferation and apoptosis, levels of intracellular reactive oxygen species （ROS） and cell senescence of RPEs were evaluated, qRT-PCR technology was used to assess the STAT3-mRNA. Furthermore, STAT3 overexpressed in ARPE-19 cells and the cells were pre-treated with ulcotinamide, and interfered with H2O2 and ox-LDL. The proliferation, apoptosis, ROS level and cell senescence were analyzed to know the effects of STAT3 on RPE against oxidative stress. Results Compared with the control group ,H2O2 and ox-LDL could increase the ROS level and promote the cell senescence, and the proliferation was obviously decreased, and the apoptosis significantly increased （ all P 〈 0.05 ）. Under oxidative stress, the STAT3-mRNA expression was increased and the expression density of ox-LDL and H202 were 3.3 ± 1.2 and 3.5± 1.1 ,respectively, there were statistical differences compared with control group （ all P 〈 0.05 ）. STAT3 could protect cells from oxidative stress damage, increased cell proliferation, decreased apoptosis and ROS accumulation;But could not modulate the cell senescence during oxidative stress. Conelusion STAT3 can anti-oxidative stress damage independently, and prompt the application of STAT3 in the treatment of AMD.

关 键 词：氧化低密度脂蛋白 信号转导/转录激活因子3 人视网膜色素上皮细胞-19 细胞衰老 活性氧族 

分 类 号：R774[医药卫生—眼科]