新型非酒精性脂肪肝模型建立及免疫细胞机制探讨  

New method of non-alcoholic fatty liver disease mouse models and mechanism about immune cells

作　　者：陈一平 肖百全 张景鸿[4,2] 刘位位 肖亚强 李超乾 CHEN Yi-ping;XIAO Bai-quan;ZHANG Jing-hong;LIU Wei-wei;XIAO Ya-qiang;LI Chao-qian(Geriatric Dept,the Affiliated Minzu Hospital of Guangxi Medical University/Guangxi Minzu Hospital, Nanning 530001, China;Center for Drug of Non-clinical Evaluation Research,Guangdong Institute of Applied Biological Resources, Guangzhou 510990, China;Emergency Dept,the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;Talents Highland of Emergency and Medical Rescue of Guangxi Province in China, Nanning 530021,China;Guangxi Medical University Graduate School, Nanning 530021, China;Medical Dept,Guangxi Medical College, Nanning 530023,China)

机构地区：[1]广西医科大学附属民族医院/广西民族医院老年病科,广西南宁530001 [2]广西急诊与医学救援人才小高地,广西南宁530021 [3]广东省生物资源应用研究所药物非临床评价研究中心,广东广州510990 [4]广西医科大学第一附属医院急诊科,广西南宁530021 [5]广西医科大学研究生院,广西南宁530021 [6]广西卫生职业技术学院医学系,广西南宁530023

出　　处：《中国药理学通报》2018年第6期882-886,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81360007);广西急诊与医学救援人才小高地开放课题资助项目(No GXJZ201507)

摘　　要：目的 建立小鼠非酒精性脂肪肝模型,并探讨肝脏不同淋巴细胞在该模型中的作用。方法 选用C57BL/6J小鼠,随机分为对照组(基础饲料)和模型组(基础饲料联合肠内营养液灌胃),实验12周及16周时,测定小鼠体质量、肝指数、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)水平,病理学检查观察肝脏脂肪浸润表现。造模16周后,流式细胞术检测肝脏自然杀伤(NK)细胞、辅助性T(Th)细胞、自然杀伤T(NKT)细胞数量及IL4+自然杀伤T(NKT)细胞。结果 模型组小鼠肝指数、TC、LDL、ALT、AST水平明显增高(P<0.05)。病理学切片显示,肝脏脂肪沉积明显,脂质滴分布于整个小鼠肝脏。NKT细胞数目明显增加(P<0.05),IL4^+NKT细胞数目增加更为明显(P<0.01)。结论 通过基础饲料联合肠内营养液灌胃的方法能成功构建中重度非酒精性脂肪肝模型。在小鼠非酒精性脂肪肝模型中,NKT细胞数量明显增加,活性明显增强,可能是该疾病的治疗新靶点。Aim To establish non-alcoholic fatty liver disease mouse model and study different kinds of lymphocytes in C57BL/6J mouse model. Methods SPF male C57BL/6J mice were randomly divided into control group（normal diet） and model group（normal diet with high fat diet by gavage）. Models of non-alcoholic fatty liver disease were established. At 12 th and 16 th weeks,body weight,liver index,serum TC,TG,HDL,LDL,ALT,AST were measured. Pathological examination of fat deposition in liver was performed. Flow cytometry was used to assay the percentage of natural killer cells,T helper cells,natural killer T cells and IL4＋NKT cells in mouse liver. Results Liver index,serum TC,LDL,ALT,AST were significantly higher in model group（P 〈 0. 05） after 16 weeks. Pathological sections showed that liver fat deposition in model group was quite severe and large lipid droplets spread through the mouse liver.The percentage of natural killer T cells increased significantly（P 〈 0. 05） and the percentage of IL4＋NKT cells increased even more obviously（P 〈 0. 01）. Conclusions C57BL/6J mice fed with normal diet and high fat diet by gavage can form a good non-alcoholic fatty liver disease mouse model. In this model,the number and activity of natural killer T cells are significantly changed,and natural killer T cells may be the new target of the mechanism and drug treatment of nonalcoholic fatty liver disease.

关 键 词：非酒精性脂肪肝 动物模型 小鼠 NKT细胞 NK细胞 TH细胞 

分 类 号：R-332[医药卫生] R322.47