细粒棘球蚴感染早期对小鼠肝脏NKT细胞及其相关因子的影响  

Effects of Echinococcus granulosus infection on liver natural killer T(NKT)cells and related factors in mice in early stage

作　　者：康雪娇 邓冰清 李寅时 王慧 张传山[1,2] 李静 KANG Xuejiao;DENG Bingqing;LI Yinshi;WANG Hui;ZHANG Chuanshan;LI Jing(School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830054,China;Institute of Clinical Medicine,The First Affiliated Hospital of Xinjiang Medical University,State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Urumqi 830054,China;Laboratory of High Incidence Disease Research in Xinjiang,Urumqi 830054,China;Xinjiang Uygur Autonomous Region Key Laboratory of Molecular Biology for Endemic Diseases,Urumqi 830054,China)

机构地区：[1]新疆医科大学基础医学院,乌鲁木齐830054 [2]新疆医科大学第一附属医院临床医学研究院,省部共建中亚高发病成因与防治国家重点实验室,乌鲁木齐830054 [3]新疆地区高发疾病研究教育部重点实验室,乌鲁木齐830054 [4]新疆维吾尔自治区地方病分子生物学重点实验室,乌鲁木齐830054

出　　处：《新疆医科大学学报》2024年第5期653-659,共7页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金项目(2022D01E51);国家自然科学基金项目(82060370);新疆地区高发疾病研究教育部重点实验室开放课题资助项目(2023B03)。

摘　　要：目的探讨细粒棘球蚴感染早期对小鼠肝脏自然杀伤T(Natural killer T,NKT)细胞及其相关因子的影响。方法将24只雌性C57BL/6小鼠随机分为对照组与感染组,每组12只。感染组经肝门静脉接种细粒棘球蚴原头蚴,对照组注射等量生理盐水,4周后,每组各取6只小鼠的肝脏组织进行Masson染色,另外6只小鼠的肝脏组织用于分离淋巴细胞以进行流式细胞术检测小鼠肝脏不同NKT细胞亚群比例和相关细胞因子干扰素-γ(Interforn-γ,IFN-γ)、肿瘤坏死因子-α(Tumour necrosis factor-α,TNF-α)、白细胞介素-4(Interleukin-4,IL-4)、白细胞介素-10(Interleukin-10,IL-10)和白细胞介素-17A(Interleukin-17A,IL-17A)的表达。结果与对照组纤维占比比较,感染组肝脏侵袭部位及其邻近肝脏组织呈现结缔组织病变,纤维化明显,纤维占比显著增加,且分布较广,包绕肉芽肿四周形成条索状纤维间隔。与对照组比较,感染组小鼠肝脏NKT细胞比例和CD4^(+)NKT细胞比例显著降低,差异均有统计学意义(P均<0.01);与对照组比较,感染组小鼠肝脏NKT细胞分泌TNF-α的比例、CD4^(+)NKT细胞分泌TNF-α的比例显著升高,差异均有统计学意义(P<0.05)。结论细粒棘球蚴感染早期小鼠肝脏纤维化程度增加,肝脏NKT细胞及其亚群CD4^(+)NKT细胞产生TNF-α的水平增加,提示肝脏NKT细胞可能参与细粒棘球蚴感染早期肝脏免疫应答反应。Objective To investigate the early effects of Echinococcus granulosus infection on natural killer T(NKT)cells and its related factors in mouse liver.Methods 24 female C57BL/6 mice were randomly assigned to control group and infection group,with 12 mice in each.The infection group received inoculation of Echinococcus granulosus protoscoleces via the hepatic portal vein,while the control group received an equivalent volume of saline.After 4 weeks,liver tissues were harvested from 6 mice per group for Masson staining,and the tissues from the remaining mice were used to isolate lymphocytes for flow cytometry analysis of various NKT cell subsets and their cytokine expression,including interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),interleukin-10(IL-10)and interleukin-17A(IL-17A).Results Compared with control group,the invasion sites and adjacent liver tissues in the infection group showed connective tissue disease,obvious fibrosis,a significant increase in the proportion of fibers and a wide distribution of fibers,the granuloma was surrounded by a cord-like fibrous septum.Compared with control group,the ratio of NKT cells and CD4^(+)NKT cells in the liver of the infected group were decreased significantly(P<0.01),the ratio of TNF-αsecreted by NKT cells and the ratio of TNF-αwas secreted by CD4^(+)NKTcells in the liver of infected mice increased significantly(P<0.01).Conclusion In the early stage of Echinococcus granulosus infection,the degree of liver fibrosis and the level of TNF-αproduced by NKT cells and their subgroups CD4^(+)NKT cells was increased,suggesting that liver NKT cells may participate in the early liver immune response to Echinococcus granulosus infection.

关 键 词：囊型包虫病 细粒棘球蚴 肝脏 自然杀伤T细胞 

分 类 号：R383.33[医药卫生—医学寄生虫学]