利多卡因通过HMGB1/RAGE信号改善缺血性卒中大鼠血-脑脊液屏障通透性研究  

Lidocaine improves blood-cerebrospinal fluid barrier permeability in ischemic stroke rats through HMGB1/RAGE signaling

作　　者：居热提·库德热提[1] 艾力克木·艾合买提 张宇轩[1] 徐桂萍[1] Jureti Kudereti;Alikemu Aihemaiti;Zhang Yuxuan;Xu Guiping(Department of Anesthesia,People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院麻醉科,新疆麻醉管理临床医学研究中心,乌鲁木齐830000

出　　处：《脑与神经疾病杂志》2023年第11期687-692,共6页Journal of Brain and Nervous Diseases

基　　金：新疆维吾尔自治区卫生健康青年医学科技人才专项(WJWY-202203)。

摘　　要：目的探讨利多卡因对缺血性卒中模型大鼠血-脑脊液屏障(BCFB)的影响及其机制研究.方法100只雄性健康的SD大鼠,随机分为假手术组(Sham),缺血性卒中组(MCAO),利多卡因低、中、高剂量组(Lidoc-L,M,H,1 mg·kg^(-1),5 mg·kg^(-1),10 mg·kg^(-1)).采用Longa线栓法构建中动脉缺血(middle cerebral artery occlusion,MCAO)模型,静脉注射不同剂量的利多卡因,2 h后拔出线栓恢复缺血区血流灌注.24h后,参考Longa-Zea标准进行神经功能评分.将大鼠处死,取全脑组织分别开展脑梗死区域染色,BCFB通透性检测,脑水肿程度检测,取缺血侧脑组织分别进行mRNA与蛋白表达检测.结果与Sham组相比,MCAO组大鼠神经功能评分、脑梗死体积、透过BCFB的伊文思蓝含量与脑水肿程度明显增加(P<0.05),HMGB1与RAGE的mRNA与蛋白表达明显增加(P<0.05),凋亡蛋白Cleaved-Caspase-3、Bax蛋白表达增加(P<0.05),BCFB紧密连接蛋白Claudin-5与ZO-1蛋白表达减少(P<0.05);与MCAO组相比,Lidoc-M与Lidoc-H组大鼠神经功能评分、脑梗死体积、透过BCFB的伊文思蓝含量与脑水肿程度明显减少(P<0.05),高迁移率族蛋白B1(HMGB1)与糖基化终产物受体(RAGE)的mRNA与蛋白表达明显减少(P<0.05),凋亡蛋白Cleaved-Caspase-3、Bax蛋白表达减少(P<0.05),BCFB紧密连接蛋白Claudin-5与ZO-1蛋白表达增加(P<0.05).结论利多卡因可能通过HMGB1/RAGE信号以通路保护BCFB紧密连接完整性,发挥抗缺血性卒中作用.Objective To investigate the effects of lidocaine on blood-cerebrospinal fluid barrier(BCFB)in ischemic stroke model rats and its mechanism.Methods 100 male healthy SD rats were randomly divided into Sham group,MCAO group,lidocaine low-dose,medium-dose and high-dose groups(Lidoc-L,M,H,1 mg·kg^(-1),5 mg·kg^(-1),10 mg·kg^(-1)).The Middle cerebral artery occlusion(MCAO)model was established by using Longa method.Different doses of lidocaine were injected intravenously.After 2 hours,the thread was removed to restore blood perfusion in the ischemic area.24h later,Longa-Zea criteria was used to evaluate neural function.The rats were sacrificed,and the whole brain tissues were stained for cerebral infarction areas,and the BCFB permeability and the degree of cerebral edema were detected.mRNA and protein expression were detected for ischemic side brain tissues.Results Compared with Sham group,neural function score,cerebral infarction volume,Evans blue content through BCFB and cerebral edema of rats in MCAO group significantly increased(P<0.05),mRNA and protein expressions of HMGB1 and RAGE significantly increased(P<0.05).Expression of apoptotic proteins Cleaved Caspase-3 and Bax increased(P<0.05),and expression of BCFB tight junction proteins Claudin-5 and ZO-1 decreased(P<0.05).Compared with MCAO group,neurological function score,cerebral infarction volume,Evans blue content through BCFB and cerebral edema of rats in Lidoc-M and Lidoc-H groups significantly decreased(P<0.05),mRNA and protein expressions of HMGB1 and RAGE significantly decreased(P<0.05).Expression of apoptotic proteins Cleaved Caspase-3 and Bax decreased(P<0.05),and expression of BCFB tight junction proteins Claudin-5 and ZO-1 increased(P<0.05).Conclusion Lidocaine may protect the integrity of tight junction of BCFB through HMGB1/RAGE signal and play an anti-ischemic stroke role。

关 键 词：利多卡因 缺血性卒中 血-脑脊液屏障 神经凋亡 剂量 

分 类 号：R743.32[医药卫生—神经病学与精神病学]