D半乳糖诱导的衰老小鼠胸腺的结构变化及功能评价  

Structural changes and functional evaluation of the thymus in aging mouse induced by D-galactose

作　　者：黄闰 梁嘉钰 罗闯 杨佳丽 陈环 谢翔 HUANG Run;LIANG Jiayu;LUO Chuang;YANG Jiali;CHEN Huan;XIE Xiang(Public Center of Experimental Technology,The school of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学基础医学院,西南医科大学公共实验技术中心,四川泸州646000

出　　处：《细胞与分子免疫学杂志》2022年第10期898-903,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81800670);泸州市人民政府-西南医科大学科技战略合作项目(2020LZXNYDZ05)。

摘　　要：目的探究D半乳糖诱导的衰老小鼠胸腺的结构变化和功能改变,并探索合适的胸腺衰老小鼠模型建立方法。方法首先建立不同给药剂量胸腺衰老小鼠模型,雌性C57BL/6小鼠随机分为对照组、[500 mg/(kg·d)]D半乳糖处理组和[1000 mg/(kg·d)]D半乳糖处理组,每组8只。D半乳糖处理组小鼠每天颈背部皮下注射D半乳糖500 mg/kg和1000 mg/kg,对照组小鼠每天注射等量生理盐水。连续给药56 d后,处死小鼠取胸腺观察胸腺大体形态并计算胸腺指数,HE染色法观察胸腺结构,流式细胞术检测胸腺CD4、CD8阳性细胞比例评价胸腺免疫功能。随后建立不同处理时长胸腺衰老小鼠模型,将雌性C57BL/6小鼠随机分为对照组和[1000 mg/(kg·d)]D半乳糖处理组,每组24只。分别在处理后的6周、9周、12周后处死小鼠,HE染色观察胸腺结构,ELISA测定血浆中胸腺素β4、胸腺肽α1、胸腺生成素含量。结果D半乳糖处理可诱导小鼠胸腺衰老,胸腺萎缩,胸腺指数减小,胸腺结构紊乱且免疫功能受损。其中[1000 mg/(kg·d)]D半乳糖处理组小鼠胸腺髓质区萎缩更加明显且皮髓质区分界消失,CD4^(+)CD8^(+)胸腺细胞减少,CD4^(+)CD8^(-)胸腺细胞增加。在不同处理时长胸腺衰老小鼠模型中,胸腺萎缩,胸腺指数减小,胸腺髓质区萎缩,皮髓质区分界不清,血浆中胸腺肽α1减少,胸腺分泌功能受损。胸腺衰老现象在D半乳糖处理12周后最明显。结论D半乳糖可诱导小鼠胸腺萎缩,胸腺指数减小,胸腺髓质区萎缩,皮髓质分界不清,致使胸腺免疫功能和分泌功能受损。每天颈背部皮下注射1000 mg/kg D半乳糖,连续十二周是建立胸腺衰老模型的合适方法。Objective To explore the structural changes and functional changes of the thymus in aging mouse induced by D-galactose,and to explore a suitable method for establishing an aging mouse model of the thymus.Methods Thymus aging mouse models were established,female C57BL/6 mice were randomly divided into control group,[500 mg/(kg·d)]D-galactose treatment group,and[1000 mg/(kg·d)]D-galactose treatment group,with 8 mice in each group.The mice in the D-galactose treatment group were injected with 500 mg/kg and 1000 mg/kg of D-galactose subcutaneously on the back of the neck every day,while the mice in the control group were injected with the same amount of normal saline every day.After 56 days of continuous administration,the mice were sacrificed to take the thymus to observe the gross thymus morphology and calculate the thymus index.Then the thymus structure were observed by HE staining,and CD4/CD8 positive thymocytes were detected by flow cytometry to evaluate the immune function of the thymus.Later,thymus aging mouse models with different treatment time were established.Female C57BL/6 mice were randomly divided into control group and[1000 mg/(kg·d)]D-galactose treatment group,with 24 mice in each group.The mice were sacrificed after 6 weeks,9 weeks,and 12 weeks treatment.The structure of thymus was observed by HE staining.The contents of thymosin β4,thymosinα1,and thymopoietin in plasma were determined by ELISA.Results D-galactose treatment can induce mouse thymus senescence,atrophy of thymus,decrease of thymus index,disorder of thymus structure and impaired immune function.In the[1000 mg/(kg·d)]D-galactose treatment group,the atrophy of the thymic medulla of mice was more obvious,with the disappeared cortical and medullary boundary,decreased CD4^(+)CD8^(+)thymocytes and increased CD4^(+)CD8^(-)thymocytes.The thymus aging mouse models with different treatment time showed the atrophied thymus,decreased thymus index,constricted thymus medulla,blurred boundary of cortex and medulla,decreased plasma thymosinα1 and

关 键 词：胸腺衰老 D半乳糖 胸腺素β4、胸腺肽α1、胸腺生成素 衰老小鼠模型 

分 类 号：R339.38[医药卫生—人体生理学] R322.53[医药卫生—基础医学] R392.9