摘要
目的探讨依达拉奉对缺血性脑卒中大鼠血脑屏障的影响及其机制。方法取Wistar大鼠,采用Longa线栓法构建脑缺血再灌注(I/R)模型。次日评估大鼠神经功能,随机分为脑缺血再灌注组(I/R-24h、I/R-7d)、依达拉奉低剂量组(Eda-L组)和依达拉奉高剂量组(Eda-H组),每组12只。除I/R-24h组大鼠行为学检测完成后处死,其余大鼠尾静脉注射依达拉奉或生理盐水,连续每天给药(7 d)后,再次评估神经功能评分。大鼠处死并取脑组织,采用2,3,5-氯化三苯基四氮唑(TTC)法检测大鼠脑梗死体积,干湿重法检测脑组织含水量,伊文思蓝(EB)示踪法检测血脑屏障完整性,试剂盒检测氧化应激因子,Western blot检测基质金属蛋白酶9(matrix metallopeptidase 9,MMP-9)、紧密连接跨膜蛋白5(Claudin-5)、封闭蛋白(Occludin)蛋白表达。结果I/R导致大鼠神经功能评分升高,出现脑梗死区域。与Sham组相比,I/R组大鼠脑组织中EB含量与水肿程度明显增加。然而与I/R组相比,Eda-H组神经功能评分与梗死面积减少,EB穿透率降低,水肿程度回调至基线。此外,与I/R组相比,Eda-H组氧化应激因子含量减少,MMP-9蛋白表达增加,且Claudin-5与Occludin蛋白表达增加。结论依达拉奉通过提高氧自由基清除,下调MMP-9表达水平,促进血脑屏障修复,改善大鼠神经功能与脑水肿。
Objective To investigate the effect of edaravone on the blood-brain barrier in rats with ischemic stroke and related mechanism.Methods A model of cerebral ischemia-reperfusion in Wistar rats was established through the Longa method.The nervous function of these rats were established on the next day.Then,the rats were randomly divided into the following groups(n=12):two cerebral ischemia/reperfusion groups(group I/R-24 h and group I/R-7 d),a low-dose edaravone group(group Eda-L)and a high-dose edaravone group(group Eda-H).The rats in group I/R-24 h were sacrificed after the behavioral test.Rats in other groups were injected with edaravone or normal saline via the tail vein once daily for consecutive seven days,and then the neurological function scores were re-evaluated.The rats were sacrificed and their brain tissues were collected.The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride(TTC)method.The water content was examined by dry and wet weight method.The integrity of the blood-brain barrier was detected by Evans blue(EB)trace method.The levels of oxidative factors were measured by ELISA kits.The levels of MMP-9,Claudin-5,and Occludin were detected by Western blot.Results I/R caused increases in neurological function scores in rats,with infarction in the brain.Compared with group Sham,group I/R showed remarkable increases in EB content in the brain tissue and water content.However,compared with group I/R,group Eda-H presented significantly decreased neurological scores and infarct area,with reduced EB penetrating rate and the water content restored to the baseline.In addition,compared with I/R group,group Eda-H showed reduced contents of oxidative stress factors and increased levels of MMP-9,Claudin-5 and Occludin.Conclusions Edaravone can enhance the scavenging of oxygen free radicals,dow-regulate the level of MMP-9,promote the repair of the blood-brain barrier,and improve the neurological function and cerebral edema in rats.
作者
孙春梅
唐玲
庹玉平
SUN Chunmei;TANG Ling;TUO Yuping(Department of Pharmacy,the Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China)
出处
《徐州医科大学学报》
CAS
2022年第8期583-587,共5页
Journal of Xuzhou Medical University
基金
四川省卫生健康委员会科研课题(19PJ044)。
关键词
依达拉奉
缺血性卒中
血脑屏障
氧化应激
edaravone
ischemic stroke
blood-brain barrier
oxidative stress
