树鼩感染HEV致中枢神经损伤与IL-4和IL-5表达相关性研究  

Correlation between the expression of IL-4 and IL-5 and central nervous system injury caused by HEV infection in tree shrews

作　　者：朱培英 杨国琴 宋春莲 付忠海 孙以鑫 武鑫 柴俊 李文贵 ZHU Peiying;YANG Guoqin;SONG Chunlian;FU Zhonghai;SUN Yixin;WU Xin;CHAI Jun;LI Wengui(College of Animal Medicine,Yunnan Agricultural University,Kunming 650201,China;School of Biotechnology and Engineering,West Yunnan Normal University of Science and Technology,Lincang 677000,China)

机构地区：[1]云南农业大学动物医学院,云南昆明650201 [2]滇西科技师范学院生物技术与工程学院,云南临沧677000

出　　处：《中国兽医科学》2024年第3期403-409,共7页Chinese Veterinary Science

基　　金：云南省猪重要疫病防控技术体系构建及应用项目(202102AE090007);云南省兽医公共卫生国际联合研发中心项目(2023BI60619)。

摘　　要：戊型肝炎病毒(HEV)感染人可引起神经系统等肝外损伤,其机理尚不清楚。本研究经腹腔注射建立HEV树鼩实验感染模型后,采用RT-PCR法检测粪便、肝和脑等组织中HEV负链RNA,实时荧光定量PCR检测感染树鼩脑、粪便、小肠以及肝中病毒的消长,测定谷草转氨酶(AST)、谷丙转氨酶(ALT)水平。组织病理学观察各组织的损伤情况以及炎症因子IL-4、IL-5在不同感染时间段的表达水平。结果显示,感染第7天全部组织均能检测到病毒负链RNA的复制;AST、ALT与对照组相比明显升高。组织病理学观察发现肝等组织出现不同程度的损伤,脑膜扩张充血,胶质细胞浸润,小脑出现大量空泡样结构、白质充血,脊髓内各类神经元形状大小不一,神经元广泛变性坏死、胞核崩解固缩,伴有胶质细胞增生。IL-4和IL-5 m RNA转录水平在感染早期和中期均有明显的升高。结果表明,HEV可突破血脑屏障进入脑和脊髓等实质组织,并引起脑和脊髓的病理损伤,感染早期IL-4和IL-5在不同组织有不同程度的升高,与HEV感染引起的脑和脊髓等组织的损伤有关联。Hepatitis E virus(HEV) can cause extrahepatic injury of the nervous system,but its mechanism is still unclear.The experimental infection model of HEV tree shrew was established by intraperitoneal injection.RT-PCR was used to detect HEV negative strand RNA in feces,liver,brain and other tissues,real-time fluorescence quantitative PCR was used to detect the growth and decline of virus in brain,feces,small intestine and liver of infected tree shrews,the levels of AST and ALT were determined,and histopathology was performed to observe the damage of each tissue.And the expression levels of inflammatory cytokines IL-4 and IL-5 in different time periods of infection.The results showed that the virus negative strand RNA replication could be detected in all tissues on the 7 days post infection(DPI).AST and ALT enzymes were significantly increased compared with control group.Histopathological observation revealed that the liver and other tissues were damaged to different degrees,meninges were dilated and congested,glial cells infiltrated,cerebellum showed a large number of vacuole-like structures and white matter congestion,and various types of neurons in the spinal cord had different shapes and sizes,with more neurons becoming denaturated and necrosis,nucleus disintegration and contraction,and glial cell hyperplasia.IL-4 and IL-5 m RNA transcription levels increased significantly in the early and middle stages of infection.The results show that HEV can break through the blood-brain barrier and enter the parenchymal tissues such as brain and spinal cord,and cause pathological injury of brain and spinal cord.IL-4 and IL-5 increase in different tissues in the early stage of infection,which is related to the injury of brain and spinal cord tissues caused by HEV infection.

关 键 词：戊型肝炎 树鼩 中枢神经损伤 IL-4 IL-5 

分 类 号：S852.659.6[农业科学—基础兽医学]