槲皮素对奈瑟球菌感染脑膜炎大鼠脑保护作用的研究  

Protective Effect of Quercetin on the Brain of Neisseria Meningitides-infected Rats

作　　者：王旭东[1] 朱海生[1] 李晓蕾[1] 麻瑞娟 WANG Xudong;ZHU Haisheng;LI Xiaolei;MA Ruijuan(Handan Central Hospital,Handan 056001,China)

机构地区：[1]邯郸市中心医院,河北邯郸056001

出　　处：《西部中医药》2024年第4期23-27,共5页Western Journal of Traditional Chinese Medicine

基　　金：邯郸市科学技术研究与发展计划(1823208082ZC)。

摘　　要：目的:探讨槲皮素(Quercetin,Que)对奈瑟球菌感染脑膜炎大鼠脑组织的保护作用及其机制。方法:将180只SD大鼠随机分为正常对照组,模型组,氨苄青霉素(AMP组,200 mg/kg)组,Que低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组,每组30只。除正常对照组外,其余各组大鼠均采用小延髓池注射奈瑟球菌悬液的方法制备脑膜炎大鼠模型。造模后,各组均每12 h给药1次(AMP皮下注射给药,Que灌胃给药),共给药5次。统计各组大鼠存活率,进行症状评分,伊文思蓝渗透法检测血脑屏障(blood-brain barrier,BBB)通透性,HE染色法行脑组织病理学检查,ELISA法检测血浆脂多糖(lipopolysaccharide,LPS)含量和脑组织肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、白细胞介素6(interleukin-6,IL-6)含量,生化分析法检测丙二醛(malondialdehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)活性,Western blot法检测脑组织p65、IκBα、HMGB1蛋白表达。结果:与模型组比较,AMP组和Que中、高剂量组大鼠存活率显著升高且症状评分、伊文思蓝渗透量降低(P<0.01);脑组织病理学改变明显改善;血浆LPS含量和脑组织TNF-α、IL-1β、IL-6、MDA含量降低,SOD、CAT活性升高(P<0.05或P<0.01);p65、HMGB1相对表达量降低而IκBα相对表达量升高(P<0.01)。与AMP组比较,Que高剂量组大鼠存活率升高,症状评分和伊文思蓝渗透量降低(P<0.05或P<0.01);血浆LPS含量和脑组织TNF-α、MDA含量降低,SOD活性升高(P<0.05或P<0.01);p65、HMGB1表达量显著降低且IκBα相对表达量升高(P<0.05或P<0.01)。结论:Que能够通过降低LPS水平、抑制NF-κB炎症通路、下调HMGB1表达、改善抗氧化酶活性,降低脑组织炎症反应和氧化应激损伤,进而达到保护奈瑟球菌感染脑膜炎大鼠脑组织的作用。Objective:To investigate the protective effect of quercetin(Que)on the brain tissue of rats with Neisseria meningitidis and its mechanism.Methods:All 180 SD rats were randomly divided into normal control group,model group,ampicillin(AMP group,200 mg/kg)group,low(50 mg/kg),medium(100 mg/kg),and high(200 mg/kg)dosage groups of Que,with 30 rats in each group.Except for the normal control group,the rat model of meningitis was prepared by injecting Neisseria suspension into the small medulla oblongata pool in all groups.After modeling,each group was administered(AMP by subcutaneous injection,Que administered by gavage)once every 12 h for a total of five times.To perform symptom scoring after collecting survival rates of rats in each group,to detect blood-brain barrier(BBB)permeability using Evans blue penetration method,to carry out brain tissue pathological examination using HE staining method,and to detect the contents of plasma lipopoly-saccharide(LPS)and tumor necrosis factor-α(TNF-α),Interleukin-1β(IL-1β)and Interleukin-6(IL-6)in brain tissue using ELISA method,to measure the contents of malondialdehyde(MDA),the activity of superoxide dismutase(SOD)and catalase(CAT)using biochemical analysis,and Western blot was used to measure the expressions of p65,IκBαand HMGB1 protein in brain tissue.Results:Compared with the model group,the survival rates of rats in the AMP group,medium and high dose groups of Que were higher,the symptom scores and Evans blue infiltration were lower(P<0.01);the pathological changes of brain tissues were improved;the contents of plasma LPS,the levels of TNF-α,IL-1β,IL-6 and MDA were lower,and the activities of SOD and CAT were higher(P<0.05 or P<0.01);the relative expressions of p65 and HMGB1 were decreased while the relative expression of IκBαwas increased(P<0.01).Compared with the AMP group,rats in the high-dose group of Que showed the noticeably higher survival rate,the lower symptom scores and Evans blue infiltration(P<0.05 or P<0.01);lower contents of plasma LPS and reduced con

关 键 词：槲皮素 奈瑟球菌 脑膜炎 脂多糖 炎症 大鼠 动物实验 

分 类 号：R378.15[医药卫生—病原生物学]