副猪链球菌临床分离株引起小鼠大脑炎性反应的特征及机制研究  

Characteristics and mechanism of cerebral inflammatory response induced by clinical Streptococcus parasuis strains in mice

作　　者：齐可欣 易雪丽[2] 王鸣柳[3] 王建平[1] 孙晖[1] 郑翰[1] Qi Kexin;Yi Xueli;Wang Mingliu;Wang Jianping;Sun Hui;Zheng Han(National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102200,China;Center for Clinical Laboratory Diagnosis and Research,The Affiliated Hospital of Youjiang Medical University for Nationalities,Youjiang 533000,Guangxi,China;Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control,Nanning 530028,Guangxi,China)

机构地区：[1]中国疾病预防控制中心传染病预防控制所,传染病预防控制国家重点实验室,北京市102200 [2]广西壮族自治区右江民族医学院附属医院,广西百色市533000 [3]广西壮族自治区疾病预防控制中心,广西南宁市530028

出　　处：《疾病监测》2023年第3期351-357,共7页Disease Surveillance

基　　金：传染病重大专项课题(No.2017ZX10303405-002);国家自然科学基金(No.81572044);传染病预防控制国家重点实验室面上课题(No.2022SKLID208);2021年度广西高校中青年教师科研基础能力提升项目(2021KY0545)。

摘　　要：目的研究副猪链球菌临床分离株引起小鼠大脑炎性反应的特征及其机制。方法副猪链球菌临床分离株NN1和BS26及高致病型猪链球菌P1/7感染C57BL/6小鼠后,观察其脑组织中的细菌载量,并提取脑组织RNA,使用实时荧光定量聚合酶链式反应方法明确诱导型一氧化氮合酶(iNOS)、促炎性细胞因子IL-1β以及核苷酸结合寡聚化结构域样受体(NOD1/2)表达的时间动力学特征。副猪链球菌临床分离株NN1和BS26及猪链球菌P1/7分别与小鼠原代星型胶质细胞及小胶质细胞细胞系BV2细胞相互作用后,分别测定细胞上清液中一氧化氮(NO)浓度以及IL-1β和NOD1/2 mRNA转录水平的时间动力学特征。结果副猪链球菌临床分离株感染小鼠后可在小鼠脑组织中持续存在超过48 h,并在感染早期引起小鼠脑组织中iNOS、IL-1β及NOD1/2受体转录水平的显著升高(P<0.05)。小胶质细胞可能在副猪链球菌临床分离株诱导脑组织产生NO和IL-1β中发挥重要作用。副猪链球菌通过NOD1/2受体激活星形胶质细胞的能力显著强于小胶质细胞(P<0.05)。结论副猪链球菌临床分离株NN1和BS26在感染早期通过产生大量NO和IL-1β等炎性介质引起小鼠大脑炎性反应和损伤,NOD1/2受体参与了副猪链球菌临床分离株诱导的小鼠大脑炎性反应。星形胶质细胞和小胶质细胞在副猪链球菌临床分离株诱导的上述炎性反应中发挥了重要作用,且副猪链球菌激活星形胶质细胞和小胶质细胞的机制存在差异。Objectives To understand the characteristics and mechanism of the cerebral inflammatory response induced by clinical Streptococcus parasuis strains in mice.Methods The bacterial loads,kinetics of inducible nitric oxide synthase(iNOS),pro-inflammatory cytokine IL-1βand NOD-like receptor(NOD1/2)transcription level in the brain of mice infected with clinical S.parasuis strain NN1,clinical S.parasuis strain BS26 and highly pathogenic Streptococcus suis(S.suis)strain P1/7 were analyzed with PCR.The NO concentration,IL-1βand NOD1/2 mRNA transcription levels of the murine primary astrocyte and microglia cell line BV2 cell infected with aforementioned three strains were also evaluated.Results Clinical S.parasuis strains NN1 and BS26 persisted in the brain of infected mice for more than 48 hours.They could upregulate the transcription level of iNOS,IL-1βand NOD1/2 mRNA in the brain of infected mice at the early phase of infection.Microglia cells might play a more important role to induce the production of NO and IL-1βin the brains of mice infected with clinical S.parasuis strains NN1 and BS26.NOD1/2 receptors were crucial for the activation of astrocytes by clinical S.parasuis strains NN1 and BS26.Conclusion Clinical S.parasuis strains NN1 and BS26 could induce the cerebral inflammatory responses at the very early phase of infection via NOD1/2 receptors.Astrocytes and microglia played an important role in the cerebral inflammatory response induced by the infection of S.parasuis clinical strains on mice.In addition,the mechanism to activate astrocyte and microglia cells by the infection of clinical S.parasuis strains varied.

关 键 词：副猪链球菌 大脑炎性反应 一氧化氮 白细胞介素-1Β 核苷酸结合寡聚化结构域样受体 星型胶质细胞 小胶质细胞 

分 类 号：R211[医药卫生—中医学] R378