郭树鹏　杨进花　赵　辉　余增洋.上海中医药大学附属岳阳医院吴泾分院药剂科，上海20024；2.上海医药工业研究院，上海200437

青葙子提取物对小鼠糖尿病视网膜病血-视网膜屏障的保护作用及机制

郭树鹏1杨进花1赵辉1余增洋2▲
1.上海中医药大学附属岳阳医院吴泾分院药剂科，上海200241；2.上海医药工业研究院，上海200437

目的观察青葙子提取物（CAE）对链脲佐菌素（STZ）诱导的C57小鼠糖尿病视网膜病（DR）血-视网膜屏障（BRB）的改善作用，并进一步研究其可能机制。方法采用STZ诱导C57小鼠建立DR模型，然后给予DR小鼠CAE 100 mg/kg干预；通过检测视网膜组织白蛋白（Albumin）渗漏和血管内皮生长因子（VEGF）表达观察CAE对DR小鼠BRB破坏的影响；采用Western blot检测视网膜组织Claudin-1、Claudin-5、Occludin、ZO-1及p-NFκB、IκB、p-IKK的蛋白表达水平；采用ELISA检测血清中TNF-α、IL-1β、IL-6含量。结果CAE能够逆转DR小鼠视网膜组织Albumin渗漏增加和VEGF表达的升高（P＜0.01）；CAE能够上调DR小鼠视网膜组织降低的紧密连接蛋白Claudin-1、Claudin-5、Occludin表达（P＜0.05或P＜0.01），同时能够抑制NFκB信号通路的激活（P＜0.01），并下调DR小鼠血清中增加的IL-1β、IL-6、TNF-α含量（P＜0.01）。结论CAE具有保护STZ诱导DR小鼠BRB的活性，其机制为保护DR中减少的紧密连接蛋白表达，同时抑制了DR中炎性信号通路的激活。

糖尿病视网膜病；青葙子；血-视网膜屏障；紧密连接蛋白；炎性信号

［Abstract］Objective To investigate the amelioration of Celosia argentea L.extract（CAE）on the blood-retina barrier（BRB）of streptozotocin（STZ）-induced diabetic retinopathy（DR），and to study its possible mechanism.Methods DR was induced by STZ injection in C57 mice and then the DR mice were given with 100 mg/kg CAE.The BRB breakdown was evaluated by the expression of Albumin leakage and VEGF.The levles of Claudin-1，Claudin-5，Occludin，ZO-1，p-NFкB，IκB and p-IKK were detected by Western blot.The levels of TNF-α，IL-1β and IL-6 in serum were quanlified by ELISA.Results The increased retinal Albumin leakage and VEGF expression were reduced by CAE in STZ-induced DR mice（P＜0.01）.The reduced retinal tight junction protein expressions of Claudin-1，Claudin-5 and Occludin were enhanced by CAE in STZ-induced DR mice（P＜0.05 or P＜0.01）.The activation of NFкB signal pathway was inhibited by CAE and further the increased serum TNF-α，IL-1β and IL-6 amount was reduced by CAE in STZ-induced DR mice（P＜0.01）.Conclusion CAE ameliorates DR via improving BRB breakdown by attenuating inflammation and enhancing the retinal tight junction protein expression.

［Key words］Diabetic retinopathy；Celosia argentea L.；Blood-retina barrie；Tight junction protein；Inflammatory signal

糖尿病视网膜病（diabetic retinopathy，DR）是糖尿病严重的并发症之一，已日渐成为影响成年人视力健康的最主要疾病。临床上根据DR的发病进展，分为早期的非增殖性糖尿病视网膜病（non-proliferative diabetic retinopathy，NPDR）和后期的增殖性糖尿病视网膜病（proliferative diabetic retinopathy，PDR）［1］。早期NPDR阶段的显著标志是血-视网膜屏障（blood-retinal barrier，BRB）的破坏和渗出增加，造成缺血缺氧状态，若得不到缓解，将进展到后期的PDR阶段，出现视网膜血管病理性增生，导致视力严重损害甚至失明［2-3］。……