摘要
目的探讨脂多糖通过导致小鼠脑细胞炎性反应诱导小鼠抑郁样行为的病理机制。方法将60只小鼠分为对照组、抑制剂组、脂多糖组、脂多糖+抑制剂组、激动剂组,每组12只。抑制剂组和脂多糖+抑制剂组腹腔注射MK801给药保护,其他组给予生理盐水,连续给药7 d后,脂多糖组和脂多糖+抑制剂组侧脑室注射脂多糖,激动剂组注射N-甲基-D天冬氨酸受体(NMDARs)激动剂,其他组给予生理盐水,小鼠麻醉恢复24 h后进行行为学实验。取小鼠完整脑组织用于Nissl染色,取小鼠海马组织用于肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6和NLRP3、含半胱氨酸的天冬氨酸蛋白水解酶-1(cleaved-caspase-1)、天冬氨酸蛋白水解酶-1(caspase-1)蛋白检测。结果行为学数据显示,脂多糖组和激动剂组小鼠产生了抑郁样行为,而脂多糖+抑制剂组小鼠抑郁样行为明显改善。脂多糖组与激动剂组小鼠海马中各项炎性细胞因子水平升高,而脂多糖+抑制剂组炎性因子水平降低。Nissl染色显示,脂多糖组和激动剂组小鼠海马神经细胞有损伤,而脂多糖+抑制剂组则明显改善了细胞损伤。此外,脂多糖组和激动剂组海马CA1区神经细胞中NLRP3和cleaved-caspase-1表达水平升高,而脂多糖+抑制剂组表达降低。结论脂多糖可通过激活NMDARs活化炎症小体NLRP3和caspase-1蛋白,促进炎性细胞因子释放,造成神经细胞损伤,诱导小鼠抑郁样行为。
Objective To investigate the pathological mechanism of lipopolysaccharide-induced inflammatory reaction and depression-like behavior in mice.Methods A total of 60 mice were divided into the control group,the inhibitor group,the lipopolysaccharide group,the lipopolysaccharide+inhibitor group and the agonist group,with 12 mice in each group.MK801 was intraperitoneally injected in advance for protection in the inhibitor group and the lipopolysaccharide+inhibitor group,the other groups received saline injections.After 7 days of continuous administration,the lipopolysaccharide group,the lipopolysaccharide+inhibitor group received an intracerebroventricular lipopolysaccharide injection,and the agonist group received an intracerebroventricular N-methyl-D-aspartate receptors(NMDARs)agonist injection,the other groups received saline injections.After the mice recovered for 24 h,the behavioral experiment was performed.Then,the whole brain tissues were taken for Nissl staining and the hippocampus tissues were collected for tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 detections and NLRP3,cleaved-caspase-1,caspase-1 expression detections.Results Depression-like behavior was observed in mice in the lipopolysaccharide group and the agonist group,while depression-like behavior in the lipopolysaccharide+inhibitor group was improved.In addition,the levels of inflammatory factors increased in the lipopolysaccharide group and the agonist group,which decreased in the lipopolysaccharide+inhibitor group.Nissl staining also showed that there was cell damage in the lipopolysaccharide group and the agonist group,while which improved in the lipopolysaccharide+inhibitor group.NMDARs agonist was similar to lipopolysaccharide in pharmacological,whose administration caused damage to hippocampal neurons.Moreover,the levels of NLRP3 and cleaved-caspase-1 increased in hippocampal neurons CA1 district of the lipopolysaccharide group and the agonist group,while which decreased in the lipopolysaccharide+inhibitor group.Conclusion Lipopolysaccharide may activate NMDARs,mature NLRP3 inflammasome and caspase-1 protein,which caused elevated levels of pro-inflammatory cytokines and lead to nerve cells damage in mice with depression-like behavior.
作者
杨建波
姜伟玲
张力三
YANG Jianbo;JIANG Weiling;ZHANG Lisan(Department of Neurology,Jiangshan People′s Hospital/Jiangshan Branch of Zhejiang University Medical College Affiliated Sir Run Shaw Hospital,Jiangshan,Zhejiang 324100,China;Department of Neurology,Zhejiang University Medical College Affiliated Sir Run Shaw Hospital,Hangzhou,Zhejiang 310016,China)
出处
《重庆医学》
CAS
2020年第1期23-28,共6页
Chongqing medicine
基金
浙江省科技计划项目(2016C33132)
