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.docVIP

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 　　[摘要] 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。 　　[关键词] 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 　　[中图分类号] R774.1 [文献标识码] A [文章编号] 1674-4721（2016）09（a）-0017-04 　　[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 sign