丙泊酚基于SIRT1/Foxo1信号缓解脑缺血再灌注造成血脑屏障损伤  

Protection of Propofol on Blood-brain Barrier Injury induced by Ischemia/Reperfusion Based on SIRT1/Foxo1 Signal

作　　者：肖志博[1] 谢海[1] 金辉[1] 王健[1] 陈锐 XIAO Zhi-bo;XIE Hai;JIN Hui;WANG Jian;CHEN Rui(Department of Anesthesiology,The First Affiliated Hospital of Hainan Medical College, Haikou 570102, China)

机构地区：[1]海南医学院第一附属医院麻醉科,海口570102

出　　处：《微循环学杂志》2022年第1期12-18,共7页Chinese Journal of Microcirculation

基　　金：海南省卫生健康委员会科研项目(20A200055)。

摘　　要：目的:探究丙泊酚是否通过激活SIRT1/Foxo1信号通路对脑缺血再灌注损伤诱导血脑屏障破坏发挥保护作用。方法:48只大鼠随机分为假手术组(Sham组),脑缺血再灌注组(I/R组),脑缺血再灌注+丙泊酚组(I/R+Propofol组),脑缺血再灌注+丙泊酚+SIRT1抑制剂EX527组(I/R+Propofol+EX527组),每组各12只。通过大鼠脑缺血120min,再灌注24h建立脑缺血再灌注模型。EX527(5mg/kg)于手术前通过蛛网膜下腔注射。丙泊酚(10mg/kg)于脑缺血过程中,尾静脉注射。再灌注24h后评估神经功能、检测脑梗死体积、血脑屏障通透性、炎性细胞因子含量、紧密连接蛋白和SIRT1/Foxo1信号相关蛋白表达情况,并比较各组间的差异。结果:与Sham组相比,I/R组神经功能障碍评分升高,脑梗死体积增加,脑组织中伊文思蓝透过率增加。与I/R组相比,I/R+Propofol组神经功能障碍评分降低,脑梗死体积减少,伊文思蓝透过率降低,脑脊液中IL-1β、IL-6含量明显减少,缺血区基底层组织中SIRT1表达增加,Ac-Foxo1、NLRP3表达减少,紧密连接蛋白Claudin-1,Occludin与ZO-1表达增加(均P<0.05)。而I/R+Propofol+EX527组上述丙泊酚脑保护作用均减弱(P<0.05)。结论:丙泊酚对脑缺血再灌注过程中血脑屏障的完整性具有保护作用,其机制可能是其能激活SIRT1/Foxo1信号通路,抑制炎症反应,增加紧密连接蛋白表达。Objective:To investigate whether propofol can protect the blood-brain barrier from cerebral ischemia-reperfusion injury by activating the SIRT1/Foxo1 signal.Method:48 rats were randomly divided into sham group(Sham),ischemia reperfusion group(I/R),ischemia reperfusion+propofol group(I/R+Propofol),ischemia reperfusion+propofol group+EX527 group(I/R+Propofol+EX527).The rats were cerebral ischemia for 120 minutes and reperfusion for 24 hours for I/R model.EX527(5mg/kg)was injected into the subarachnoid area before operation in I/R+Propofol+EX527.During cerebral ischemia,propofol(10mg/kg)was injected through tail vein.Neurological dysfunction score was evaluated after 24 hours of reperfusion,cerebral infarction volume,blood-brain barrier permeability,inflammatory cytokine content,and tight junction protein expression in SIRT1/Foxo1 signal-related proteins were detected.Results:Compared with the Sham group,the I/R group had higher neurological dysfunction scores,increased cerebral infarct volume,and increased Evans blue permeability in brain.Compared with the I/R group,the rats in Propofol group had lower neurological scores,less cerebral infarction volume,and lower Evans blue transmittance in the brain tissue.In addition,the content of IL-1βand IL-6 in the cerebrospinal fluid was significantly reduced,the expression of SIRT1 in the basal tissue of the ischemic area was increased,and the expression of Ac-Foxo1 and NLRP3 were decreased.At the same time,the expression of tight junction proteins Claudin-1,Occludin and ZO-1 were increased(all P<0.05).However,when SIRT/Foxo1 signal was blocked by EX527,the above-mentioned brain protection effects of propofol were all reserved(P<0.05).Conclusion:Propofol has a protective effect on the integrity of the blood-brain barrier during ischemia/reperfusion progress.The mechanism may be through activating the SIRT1/Foxo1 signaling pathway,inhibiting inflammation and increasing tight junction protein expression.

关 键 词：丙泊酚 脑缺血再灌注 血脑屏障 炎症反应 SIRT1 FOXO1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]