脓毒症对新生小鼠远期认知功能障碍的机制研究  

Mechanism of sepsis on long-term cognitive dysfunction in neonatal mice

作　　者：王海川 阳倩[1] 唐彬秩[1] 李茂军[1] 石伟[1] 吴青(指导)[1] WANG Haichuan;YANG Qian;TANG Binzhi;LI Maojun;SHI Wei;WU Qing(Department of Pediatrics,Sichuan Academy of Medical Sciences,Sichuan Provincial People's Hospital,Chengdu 610072,China)

机构地区：[1]四川省医学科学院·四川省人民医院儿科,成都610072

出　　处：《中国免疫学杂志》2022年第24期2958-2962,共5页Chinese Journal of Immunology

基　　金：四川省人民医院专项基金项目(2021ZX04)。

摘　　要：目的:在新生小鼠为脓毒症的情况下,观察其成年后认知功能及脑内炎症因子与Tau蛋白磷酸化水平的变化,探讨脓毒症对新生小鼠远期认知功能障碍的影响及其作用机制。方法:选取出生后5 d的C57BL/6J小鼠通过腹腔注射脂多糖(LPS)(100μg/kg)构建全身炎症反应模型,待生长至8周后观察C57BL/6J小鼠神经行为学变化,取大脑海马组织检测IL-1β、TNF-α、Tau蛋白和磷酸化Tau蛋白的表达;同时测定外周血清中IL-1β、TNF-α含量,采用免疫荧光实验观察海马组织中Tau蛋白的改变。结果:与对照组相比,实验组小鼠在行为学方面主要表现为学习记忆能力降低(P<0.05),同时伴随着海马组织中炎症因子含量上升(P<0.05),Tau蛋白和磷酸化Tau蛋白表达升高(P<0.05);与对照组相比,实验组外周血清中IL-1β、TNF-α的含量无明显差异。结论:脓毒症小鼠远期行为出现认知功能障碍可能与海马组织中炎症因子表达升高,Tau蛋白出现过度磷酸化存在关联性。Objective:To study the changes of inflammatory cytokines and Tau protein phosphorylation in the condition of systemic inflammatory response to explore the possible mechanism of long-term cognitive dysfunction.Methods:C57BL/6J mice were selected 5 d after birth to establish a systemic inflammatory response model by intraperitoneal injection of lipopolysaccharide(LPS)(100μg/kg).The neurobehavioral changes of C57BL/6J mice were observed after 8 weeks of growth.The expressions of IL-1β,TNF-α,Tau protein and phosphorylated Tau protein in the hippocampus were detected.At the same time,the levels of IL-1βand TNF-αin peripheral blood were measured,and the changes of Tau protein in hippocampus were observed by immunofluorescence assay.Results:Compared with control group,the behavior of the experimental group mainly showed that the learning and memory ability was decreased(P<0.05),and the content of inflammatory factors in the hippocampus was increased(P<0.05),and the expression of Tau protein and phosphorylated Tau protein were increased(P<0.05).Compared with the control group,there was no significant difference in the contents of IL-1βand TNF-αin the peripheral blood of the experimental group.Conclusion:The cognitive dysfunction of longterm behavior in septic mice may be related to the increased expression of inflammatory factors and the hyperphosphorylation of Tau protein in the hippocampus.

关 键 词：脓毒症 认知障碍 炎症因子 TAU蛋白 

分 类 号：R392.7[医药卫生—免疫学]