丙泊酚对脓毒症小鼠血脑屏障损伤的影响  

Effect of Propofol on Blood-Brain Barrier Damage in Septic Mice

作　　者：罗涛[1] 刘永芳[1] 刘方燕 付湘云[1] 刘志刚[1] LUO Tao;LIU Yong-fang;LIU Fang-yan;FU Xiang-yun;LIU Zhi-gang(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《神经损伤与功能重建》2022年第4期187-190,共4页Neural Injury and Functional Reconstruction

摘　　要：目的:探究丙泊酚对脓毒症小鼠血脑屏障(BBB)损伤的影响及可能的作用机制。方法:30只雄性SPF级C56BL/6小鼠随机分为对照(Con)组、脓毒症(LPS)组和丙泊酚(PF)组,每组10只。LPS组和PF组小鼠采用腹腔注射脂多糖(LPS)(10 mg/kg)制备脓毒症小鼠模型,注射LPS后的即刻和6 h后给PF组小鼠腹腔注射丙泊酚(50 mg/kg),给LPS组小鼠腹腔注射等体积的生理盐水;Con组仅给予腹腔注射等体积的生理盐水。造模24 h后,采用神经行为学评分观察小鼠行为学变化;ELISA法检测小鼠血清神经元特异性烯醇化酶(NSE)和S100β水平;伊文氏蓝(EB)法和干湿比重法检测小鼠脑组织BBB通透性和含水量;Western blot法检测脑组织闭合蛋白(Occludin)、密封蛋白(Claudin)-5和基质金属蛋白酶(MMP)-9蛋白表达量。结果:与Con组相比,LPS组小鼠神经行为学评分降低,血清NSE和S100β、脑组织含水量和EB含量明显升高,Occludin和Claudin-5表达减少,MMP-9表达增加(P<0.05);与LPS组相比,PF组小鼠神经行为学评分增高,血清NSE和S100β、脑组织含水量和EB含量明显减少,Occludin和Claudin-5明显增加,MMP-9表达降低(P<0.05)。结论:丙泊酚可减轻脓毒症小鼠BBB损伤,降低血脑屏障通透性,其机制可能与抑制MMP-9表达有关。Objective:To observe the effects of propofol on blood-brain barrier(BBB)disruption in septic mice and explore its possible mechanisms.Methods:Thirty male SPF C56BL/6 mice were randomly divided into three groups(n=10):control group(Con),sepsis group(LPS),and propofol-treated group(PF).A sepsis mouse model was established in LPS and PF group mice through intraperitoneal injections of 10 mg/kg lipopolysaccharide(LPS).Immediately and 6 hours after modeling,the PF group mice were given intraperitoneal injections of50 mg/kg propofol,and the LPS group mice were given equal volume injections of saline.Mice in the Con group were intraperitoneally injected with saline only.Twenty-four hours later,the behavioral changes of mice in the different groups were evaluated by neuroreflex scoring.Serum levels of NSE and S100β were measured by ELISA kits.The permeability of BBB and water content of brains were determined by Evans blue extravasation and the wet/dry ratio of brain tissue.The protein expression of Occludin,claudin-5,and MMP-9 were detected by Western blot to assess BBB integrity.Results:Compared with the Con group,the LPS group showed higher levels of serum NSE and S100β,water content and EB content in brain tissues,and MMP-9 protein expression and lower neuroreflex scores and decreased Occluding and Claudin-5 expression(P<0.05).Compared with that of the LPS group,the serum NSE and S100β levels,brain tissue water and EB content,and MMP-9 protein expression in the PF group were decreased,while the neuroreflex scores and Occluding and Claudin-5 expression were significantly increased(P<0.05).Conclusion:Propofol can alleviate BBB damage and decrease its permeability in septic mice,and the mechanism may involve the inhibition of MMP-9 expression.

关 键 词：脓毒症 丙泊酚 血脑屏障 基质金属蛋白酶 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]