中文摘要：

目的探讨活化转录因子4(ATM)在高糖诱导的人视网膜微血管内皮细胞(HRME&)炎症反应中的作用及机制。方法将HRME&分为正常糖组（5.5mmol/LD-葡萄糖）、高糖组（25mmd/LD-葡萄糖）、渗透压对照组（5.5mmd/LD-葡萄糖+19.5mmd/L甘露醇）、高糖+ATF4干扰组、高糖+Scmmbled组，各组的高浓度葡萄糖或甘露醇干预时间均为24h，HRME&中ATF4蛋白表达的干扰采用核糖核酸干扰技术。用蛋白免疫印迹法检测各组ATF4及炎症因子TNF-a、细胞间黏附因子-l(ICAM-l)、IL-lp、磷酸化核转录因子-KBp65(p-NF-KBp65)表达水平。用激光扫描共聚焦显微镜检测各组HRMECS的NF-KBP65核转位情况。结果与正常糖组相比，高糖组中ATF4以及炎症因子TNF-ct、ICAM-1、IL-1(3、p-NF-kBp65的表达水平均上调（P均<0.05)。渗透压对照组与正常糖组的ATF4以及炎症因子表达水平比较差异均无统计学意义（P均>0.05)。与高糖+Scrambled组相比，高糖+ATF4干扰组中ATF4以及炎症因子的表达水平均下调（P均<0.05)。与高糖组相比，高糖+ATF4干扰组中NF-kBP65核转位有所减弱。结论高糖可诱导HRME&发生炎症反应，促进NF-KBP65核转位，而敲低ATF4能减轻高糖诱导的炎症反应和NF-KBP65核转位，提示ATF4在高糖诱导的HRMECs炎症反应中起重要作用，该作用可能通过调节NF-KBP65的激活来实现。

英文摘要：

Objective To evaluate the effect and mechanism of activation transcription factor^(ATF4)upon the inflammatory response of human retinal endothelial cells(HRMECs)induced by high glucose.Methods All HRMECs were assigned into the normal glucose(5.5mmol/L D-glucose),high glucose(25mmol/L D-glucose),control(5.5mmol/L D-glucose+19.5mmol/L mannitol),high glucose+ATF4interfere and high glucose+Scrambled groups.Intervention of high glucose or mannitol was endured for24h.The expression of ATF4protein in HRMECs was interfered by ribonucleic acid interfere technique.The expression levels of ATF4,TNF-a,intercellular adherence molecule-1(ICAM-1),IL-lp,phosphorylated nuclear transcription factor-KB p65(p-NF-kB p65)were measured by western blot.The status of nucleus translocation of NF-kB p65was observed under confocal laser scanning microscopy.Results Compared with the normal glucose group,the expression levels of ATF4,TNF-a,ICAM-1,IL-1p and p-NF-kB p65were significantly up-regulated in the high glucose group(all P<0.05).No statistical significance was identified in the expressionlevels of ATF4and inflammatory cytokines between the control and normal glucose groups(all P>0.05).Compared with the high glucose+Scrambled group,the expression of ATF4and inflammatory cytokines was remarkably down-regulated in the high glucose+ATF4interfere group(all P<0.05).Compared with the high glucose group,the nucleus translocation of NF-kB p65was moderately weakened in the high glucose+ATF4interfere group.Conclusions High glucose can induce the incidence of inflammatory response of HRMECs and promote the nucleus translocation of NF-kB p65.Therefore,down-regulating the expression of ATF4is able to attenuate the high glucose-induced inflammatory response and nucleus translocation of NF-kB p65,prompting that ATF4plays a pivotal role in the inflammatory response of HRMECs induced by high glucose,which can be achieved by regulating the activation of NF-kB p65.