依达拉奉基于Wnt/β-catenin信号通路对急性脑卒中大鼠神经元增殖的影响

Effect of edaravone on neuron proliferation in acute stroke rats through Wnt/β-catenin signal

目的探讨依达拉奉对急性脑卒中大鼠神经元增殖的影响及机制。方法36只SD大鼠,随机分为对照组、模型组、依达拉奉组,每组12只。适应性喂养1w后进行急性脑卒中模型构建,次日连续给予依达拉奉进行治疗,4w后进行神经功能评分与水迷宫实验,应用免疫荧光法检测大鼠脑中神经元增殖情况,使用Western blot检测大鼠海马组织中Wnt1、GSK3β、β-catenin等蛋白表达。结果急性脑卒中造成大鼠神经功能损伤,学习记忆功能障碍。免疫荧光结果显示海马齿状回颗粒下层BrdU与DCX表达增加(P<0.05)。Western blot结果显示模型组海马组织中Wnt1、p-GSK3β、β-catenin表达增加(P<0.05)。依达拉奉组显著改善了急性脑卒中大鼠神经功能与认知功能损伤,与模型组相比,更显著增加了BrdU与DCX阳性细胞数量(P<0.05),提高了Wnt1、p-GSK3β、β-catenin表达水平(P<0.05)。结论依达拉奉通过Wnt/β-catenin信号通路促进急性脑卒中大鼠神经元增殖,改善急性脑卒中大鼠神经功能与认知功能。

Objective To explore the effect and mechanism of edaravone on neuron proliferation in acute cerebral stroke rats.Methods 36 SD rats were randomly divided into control group,model group and edaravone group,12 rats in each group.A week after adaption,Acute stroke operations were constructed,and edaravone were administrated at the next day.After 4 weeks,neurological severity scores and Morris water maze experiments were performed.Immunofluorescence was applied for neuron proliferation detection in rat brain.Western blot was used to detect the expression of Wnt1,GSK3β,β-catenin and other proteins in rat hippocampus tissue.Results Acute stroke caused neurological damage and cognition dysfunction in rats.Immunofluorescence results showed that the expression of BrdU and DCX in the dentate gyrus of the hippocampal increased(P<0.05).Western Blot results showed that in the hippocampus,the expression of Wnt1,p-GSK3βandβ-catenin of the model group increased(P<0.05).In addition,edaravone administration significantly improved the neurological function and cognition impairment in rats.Compared with the model group,it significantly increased the number of BrdU and DCX positive cells(P<0.05)and enhanced Wnt1,p-GSK3βandβ-catenin expression level(P<0.05).Conclusions Edaravone promotes neuron proliferation in rats with acute stroke through Wnt/β-catenin signaling pathway,and improves neurological and cognitive function in rats with acute stroke.