GPR124在脑缺血再灌注大鼠血脑屏障功能障碍中的作用及可能机制
The role of GPR124 in blood-brain barrier dysfunction after cerebral ischemia-reperfusion in rats and its possible mechanism
顾彩锋 1陈俊峰 1申捷1
作者信息
- 1. 复旦大学附属金山医院急危重病中心,上海 201508
- 折叠
摘要
目的 探究GPR124在脑缺血再灌注大鼠血脑屏障功能障碍中的作用及可能机制.方法 80只SD大鼠随机分为假手术组、模型组、GPR124组与GPR124+FH535组.神经功能评分判断各组大鼠的神经功能;统计脑水肿和脑梗死面积评估各组大鼠脑损伤程度;Nissl染色和H&E染色分析各组大鼠神经元的凋亡情况和海马组织的结构变化;伊文思蓝染色分析各组大鼠血脑屏障渗透性.Western blot分析GRP124对Wnt/β-catenin信号通路的影响.结果 与模型组比较,注射GRP124重组蛋白后,脑缺血再灌注损伤大鼠的神经功能缺陷评分和脑水肿程度明显降低、梗塞面积明显减少、神经元损伤程度降低、血脑屏障渗透性降低以及Wnt/β-catenin信号通路相关蛋白表达增加.联合注射GPR124+FH535后,GPR124以上的作用减弱.结论 GPR124能够改善脑缺血再灌注大鼠血脑屏障功能障碍,并且该作用可能与GPR124激活Wnt/β-catenin信号通路激活相关.
Abstract
Objective To investigate the effect of GPR124 on blood-brain barrier dysfunction in rats with cerebral ischemia-reperfusion(I/R)and its possible mechanism.Methods Eighty SD rats were randomly divided into sham operation group,model group,GPR124 group and GPR124+FH535 group.The neurological function of rats in each group was evaluated by neurological function score;the brain edema and cerebral infarction area were calculated to evaluate the degree of brain injury in each group;the apoptosis of neurons and the structural changes of hippocampal tissues were analyzed by Nissl staining and H&E staining;the permeability of blood-brain barrier was analyzed by Evans blue staining.The effect of GRP124 on Wnt/β-catenin signaling pathway was analyzed by Western blot.Results Compared with the model group,after injection of recombinant protein GRP124,the neurological function defect score,brain edema,infarct area,neuron injury,blood-brain barrier permeability and the expression of Wnt/β-catenin signaling pathway-related proteins were significantly decreased in rats with cerebral I/R injury.After combined injection of GPR124+FH535,the above effects of GPR124 were weakened.Conclusion GPR124 can improve blood-brain barrier dysfunction in rats with cerebral I/R,and this effect may be related to the activation of Wnt/β-catenin signaling pathway by GPR124.
关键词
GPR124/Wnt/β-catenin/脑缺血再灌注/血脑屏障Key words
GPR124/Wnt/β-catenin/cerebral ischemia-reperfusion/blood-brain barrier引用本文复制引用
基金项目
上海市金山区科学技术创新项目(2018-03-01)
出版年
2024
NETL
NSTL
万方数据