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

Protect effect of Celosia argentea L. for blood-retina barrier of diabetic retinopathy mice and its mechanism

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。

Objective To investigate the amelioration of Celosia argentea L. extract （GAE） 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 break- down was evaluated by the expression of Albumin leakage and VEGF. The levies of Claudin-1, Claudin-5, Occludin, ZO-1, p-NFKB, IKB 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 NFKB 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.