丙泊酚对脂多糖诱导的脓毒血症小鼠抑郁样行为和海马炎症反应的影响  

Effects of Propofol on Depression-Like Behavior and Hippocampal Inflammatory Response in Lipopolysaccharide-Induced Sepsis in Mice

作　　者：黄蕊 罗涛[1] 刘永芳[1] 胡刚[1] 刘志刚[1] 付湘云[1] HUANG Rui;LUO Tao;LIU Yong-fang;HU Gang;LIU Zhi-gang;FU Xiang-yun(Department of Anesthesiology,People’s 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》2020年第6期325-328,共4页Neural Injury and Functional Reconstruction

摘　　要：目的:观察丙泊酚预处理在脂多糖(LPS)诱导的脓毒血症小鼠抑郁样行为和海马炎症反应中的作用,并探讨其可能的作用机制。方法:60只健康ICR小鼠随机分为6组:对照组(C组),丙泊酚组(P1组),LPS组(L5组),丙泊酚+LPS组(L5P1、L5P2、L5P5组),每组10只。P1组注射10 mg/kg丙泊酚;L5组注射5 mg/kg LPS;L5P1组、L5P2组和L5P5组分别注射10 mg/kg、20 mg/kg和50 mg/kg丙泊酚预处理,30 min后注射5 mg/kg LPS。所有药物均选择腹腔注射,C组注射同等剂量的生理盐水。24 h后依次采用糖水偏好实验、悬尾实验和强迫游泳实验对小鼠进行抑郁样行为测试;行为学测试后处死小鼠,采用免疫印迹法检测脑炎性因子Toll样受体4(TLR4)、核转录因子κB(NF-κB)主要蛋白P65、髓样分化因子-2(MD-2)表达水平。结果:与C组比较,L5组糖水摄取量减少,悬尾静止时间延长,TLR4、P65、MD-2表达量升高(P<0.05)。与L5组比较,L5P1组糖水摄取量增加,TLR4、P65、MD-2表达量降低(P<0.05);L5P2组糖水摄取量增加,悬尾静止时间缩短,P65、MD-2表达量降低(P<0.05);L5P5组糖水摄取量增加,P65表达量降低(P<0.05)。结论:丙泊酚预处理可改善LPS诱导的脓毒血症小鼠抑郁样行为,降低海马炎症因子的表达,这可能与丙泊酚抑制TLR4/MD-2通路,减轻炎症反应有关。Objective:To observe the effect of propofol pretreatment on the depression-like behavior and hippocampal inflammatory response of lipopolysaccharide(LPS)-induced sepsis in mice and to explore its possible mechanism.Methods:Sixty healthy ICR mice were randomly devided into six groups(n=10):control group(group C),propofol group(group P1),LPS group(group L5),and propofol+LPS groups(groups L5P1,L5P2,and L5P5).Sepsis was induced in mice by injection with 5 mg/kg LPS.Group P1 was injected with 10 mg/kg propofol.Group L5P1,group L5P2,and group L5P5 were injected with 10 mg/kg,20 mg/kg,and 50 mg/kg propofol,respectively.After 30 minutes,mice were injected with 5 mg/kg LPS.Group C was injected with the same amount of normal saline.All injections were intraperitoneal.After 24 hours,the depression-like behavior of mice was tested by the sucrose preference test,tail suspension test,and forced swimming test.Mice were sacrificed after behavior tests;subsequently,the expression level of inflammatory factors TLR4,P65(main protein in NF-κB),and MD-2 were detected by Western blot.Results:Compared with group C,group L5 showed decreased sucrose intake,increased tail suspension time,and inceased expression of TLR4,P65,and MD-2(P<0.05).Compared with group L5,group L5P1 showed increased sucrose intake and reduced expression of TLR4,P65,and MD-2(P<0.05);group L5P2 showed decreased sucrose intake,decreased tail suspension time,and reduced expression of P65 and MD-2(P<0.05);group L5P5 showed increased sucrose intake and reduced expression of P65(P<0.05).Conclusion:Propofol can improve the depression-like behavior and reduce the expression of hippocampal inflammatory factors in LPS-induced sepsis in mice.The mechanism may be related to inhibiting the TLR4/MD-2 pathway and reducing inflammatory responses.

关 键 词：脓毒血症 丙泊酚 TOLL样受体4 

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]