中文摘要：

背景多种claudin亚型与血-视网膜屏障的功能密切相关，参与病理性新生血管的形成，从而导致多种视网膜血管性病变的发生．Claudin-23是近年来新发现的claudin亚型，研究其在视网膜中的定位、表达及其与视网膜血管病变的关系对相关病变的靶向治疗具有重要的临床意义。目的探讨氧诱导视网膜病变（OIR）小鼠视网膜中claudin-23的动态表达变化。方法将生后第7天（P7）的SPF级C57BL／6J乳鼠与母鼠放入含氧体积分数为75％±3％的密闭饲养箱中饲养5d建立小鼠OIR模型，用50g／L异硫氰酸荧光素一葡聚糖（FITC—dextran）行小鼠眶后注射并行全视网膜铺片，检测成模后缺氧小鼠的视网膜血管情况并与正常小鼠进行对照。采用实时荧光定量PCR（real—timePCR）和Westernblot法检测P12、P17和P25小鼠视网膜中claudin-23mRNA及蛋白的表达，采用real—timePCR法检测elaudin-23mRNA在小鼠视网膜中的动态表达；制备P7小鼠视网膜冰冻切片，用免疫荧光双染法检测claudin-23在正常对照组和OIR模型组小鼠视网膜中的表达定位。结果OIR模型组P17小鼠全视网膜铺片可见视网膜大血管迂曲、扩张，后极部视网膜出现无灌注区，周边部血管网状结构紊乱或消失，出现大量病理性新生血管。正常对照组小鼠随着日龄的增加，视网膜中claudin-23mRNA的表达量增加缓慢，P25时的表达量是P7时的2．3倍，蛋白表达则先增加后减少，在P12出现高峰；OIR模型组小鼠随日龄的增加claudin-23mRNA和蛋白的表达水平均快速增加，claudin-23mRNA在P25的表达量较P7增加12．5倍。正常P7小鼠与OIR模型组P7小鼠claudin-23mRNA和蛋白的表达量比较差异均无统计学意义（P〉O．05），但OIR模型组P12、P17和P25小鼠视网膜中claudin-23mRNA的表达量均明碌高于同龄正常对照组小鼠，差异均有统计学意义（P〈0．05）；P25时，elaudin．23蛋白的表达量?

英文摘要：

Background Researches showed that some claudin subtypes are closely related to the integrity of blood retina barrier and participate in pathological angiogenesis. Claudin-23 is a novel discovered eIaudin subtype. Understanding its expression in the retina and its relationship with retinal vascular lesion is very important for the targeting treatment of retinal vascular diseases. Objective The aim of this study was to investigate the differential expression of claudin-23 in the retina of mice with oxygen-induced retinopathy（ OIR）. Methods OIR mice models were established by putting postnatal day 7 （ P7 ） SPF C57BL/6J mice in the enclosed container with oxygen concentration of 75% ±3% together with mother mice for 5 days. The age-matched normal mice were used as controls. Fluorescein isothiocyanate dextran （FITC-dextran） was retro-orbitally injected to mice to confirm the models by whole-mount retina. Expressions of claudin-23 mRNA and protein in P12, P17 and P25 mice retinas were examined using real-time PCR and Western blot. Immunofluorescent staining of frozen section was used to identify the expression and location of claudin-23 in the normal and OIR mice. Results Tortuous and engorged retinal vessels were found in P17 mice retina of the OIR group. Nonperfusion zones, abnormal capillary network and lots of pathological neovascular tufts were observed on the whole-mount retinas. The level of claudin-23 mRNA was slowly inereased with the aging,reaching 2.3 fold in P25 normal mice more than P7 mice. However,that in OIR mice demonstrated 12.5- fold elevation from P7 to P25. There were no significant change in the mRNA and protein levels of claudin-23 in P7 mice retina between the normal group and OIR group（P〉0.05）. But the mRNA level of claudin-23 in P12, PI7 and P25 mice retinas was significantly higher in the OIR group than that in normal group（ P〈0.05 ）. The protein level of claudin-23 in P25 mice retina was significantly higher in the OIR group than that in normal group（ P〈0.05 ）