核苷酸结合寡聚化结构域样受体3在Ⅰ型单纯疱疹病毒性脑炎小鼠中的作用  

Role of nucleotide-binding oligomerization domain-like receptor 3 in mice with herpes simplex virus typeⅠencephalitis

作　　者：闫晓静 张娜 李静[1] 张翠林 张艳玲[1] 李磊 YAN Xiaojing;ZHANG Na;LI Jing;ZHANG Cuilin;ZHANG Yanling;LI Lei(Xingtai People's Hospital,Xingtai,Hebei 054000,China;不详)

机构地区：[1]邢台市人民医院儿科,河北邢台054000 [2]石家庄金域医学实验室,河北石家庄051430

出　　处：《中华医院感染学杂志》2025年第3期321-326,共6页Chinese Journal of Nosocomiology

基　　金：河北省医学科学研究基金资助项目(20201586);邢台市重点研发计划自筹基金资助项目(2021ZC138)。

摘　　要：目的探讨核苷酸结合寡聚化结构域样受体(NLRP)3在Ⅰ型单纯疱疹病毒性脑炎模型小鼠中的作用。方法60只SPF级雄性小鼠,其中NLRP3野生型(WT)小鼠30只,NLRP3敲除型(KO)小鼠30只,将NLRP3野生型分为WT-对照组、WT-模型组,NLRP3敲除小鼠分为KO-对照组、KO-模型组;WT-模型组、KO-模型组小鼠接种Ⅰ型单纯疱疹病毒(HSVⅠ)悬液建立病毒性脑炎(HSE)模型,接种5 d后对小鼠脑脊液进行白细胞计数、病毒滴度检测,测定脑组织水分含量与氧化应激水平,蛋白免疫印迹法检测脑组织核苷酸结合寡聚化结构域(NOD)样受体相关蛋白、氧化应激相关蛋白、T细胞亚群特异细胞因子蛋白相对表达情况。结果WT-对照组、KO-对照组小鼠状态良好,WT-模型组、KO-模型组小鼠出现眼角红肿溃烂、反应迟钝、抽搐等现象;与WT-对照组、KO-对照组相比,WT-模型组、KO-模型组小鼠脑脊液的白细胞计数(WBC)较高,脑组织湿重与含水量高,丙二醛(MDA)表达升高,干扰素(IFN)-γ、白细胞介素(IL)-4、IL-17、叉头框蛋白(FOX)P3表达水平升高,总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)表达低,核因子E2相关因子(Nrf)2、血红素氧化酶(HO)-1、醌氧化还原酶(NQO)-1降低;KO-模型组病毒滴度、脑组织湿重与含水量、MDA、FN-γ、IL-4、IL-17、FOXP3低于WT-模型组,T-AOC、SOD、Nrf2、HO-1、NQO-1高于WT-模型组(P<0.05);KO-对照组、KO-模型组小鼠的脑组织中未检出NOD样受体相关蛋白,WT-模型组NLRP3、ACS、C aspase-1表达水平高于WT-对照组(P<0.05)。结论NOD样受体表达可能与脑组织氧化应激水平有关,其在HSE模型小鼠中高表达可激活氧化应激损伤及参与细胞免疫调节。OBJECTIVE To investigate the role of nucleotide-binding oligomerization structural domain-like receptors(NODR)3 in mice with herpes simplex virus typeⅠencephalitis.METHODS Sixty SPF-grade male mice were divided into 30 NLRP3 wild-type(WT)mice and NODR3 knockout(KO)mice,and NLRP3 wild-type mice were further divided into WT-Control group and WT-Model group,and NLRP3 knockout mice were divided into KO-Control group and KO-Model group;Mice in the WT-Model and KO-Model groups were inoculated with herpes simplex virus typeⅠ(HSVⅠ)suspension to establish the viral encephalitis(HSE)Model.After 5 days of inoculation,the white blood cell(WBC)count and virus titer in the cerebrospinal fluid of mice were detected,the brain tissue moisture content and oxidative stress related index levels were determined,and the relative expression of NOD-like receptor-related proteins,oxidative stress-related proteins,and T cell subset specific cytokines proteins in the brain tissue were detected by Western blotting.RESULTS The mice in the WT-control group and KOcontrol group were in good condition,while the mice in the WT-model group and KO-model group showed redness,swollen and ulcerated corners of the eyes,unresponsiveness,and convulsions,etc..Compared with the WTcontrol group and KO-control group,the mice in the WT-model and KO-model groups had increased white blood cell(WBC)counts in cerebrospinal fluid,elevated wet weight and water content of brain tissue,elevated expression of malondialdehyde(MDA),interferon(IFN)-γinterleukin(IL)-4,IL-17,and forkhead frame protein(FOX)P3,decreased total antioxidant capacity(T-AOC)and superoxide dismutase(SOD),and decreased level of nuclear factor E2-related factor(Nrf)2,heme oxidase(HO)-1,and quinone oxidoreductase(NQO)-1.Virus titer,brain tissue wet weight and water content,MDA,IFN-γ,IL-4,IL-17,FOXP3 were lower in the KO-model group than those in the WT-model group,and T-AOC,SOD,Nrf2,HO-1,NQO-1 were higher than those in the WT-model group(P<0.05).NOD-like receptor-related proteins were not det

关 键 词：核苷酸结合寡聚化结构域样受体3 Ⅰ型单纯疱疹病毒 病毒性脑炎 氧化应激 细胞免疫 

分 类 号：R512.3[医药卫生—内科学]