中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (29): 6237-6242.doi: 10.12307/2025.799

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

脾虚型高脂血症模型小鼠的构建与评价

陈丽娟1,2,高心雪1,吴   瑾1,2,杜   莹1,2,吕美君1,2,隋国媛1,贾连群1,潘国伟3   

  1. 1辽宁中医药大学,辽宁省沈阳市  110847;2辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁省沈阳市  110847;3中国医科大学,辽宁省沈阳市  110122 

  • 收稿日期:2024-09-11 接受日期:2024-10-12 出版日期:2025-10-18 发布日期:2025-03-07
  • 通讯作者: 贾连群,博士,教授,辽宁中医药大学,辽宁省沈阳市 110847 通讯作者:潘国伟,博士,教授,中国医科大学,辽宁省沈阳市 110122
  • 作者简介:陈丽娟,女,1988年生,山东省聊城市人,汉族,硕士,实验师,主要从事中西医结合防治动脉粥样硬化基础研究。
  • 基金资助:
    国家自然科学基金项目(82204949),项目负责人:陈丽娟;辽宁省科技计划联合计划(基金)项目(2023-MSLH-192),项目负责人:陈丽娟;辽宁省教育厅面上项目(JYTMS20231813),项目负责人:陈丽娟;辽宁省教育厅高校基本科研项目储备项目(2024-JYTCB-013),项目负责人:陈丽娟;辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(zyzx2008),项目负责人:陈丽娟

Construction and evaluation of spleen-deficiency hyperlipidemia mouse models

Chen Lijuan1, 2, Gao Xinxue1, Wu Jin1, 2, Du Ying1, 2, Lyu Meijun1, 2, Sui Guoyuan1, Jia Lianqun1, Pan Guowei3   

  1. 1Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China; 2Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China; 3China Medical University, Shenyang 110122, Liaoning Province, China
  • Received:2024-09-11 Accepted:2024-10-12 Online:2025-10-18 Published:2025-03-07
  • Contact: Jia Lianqun, MD, Professor, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China Corresponding author: Pan Guowei, MD, Professor, China Medical University, Shenyang 110122, Liaoning Province, China
  • About author:Chen Lijuan, MS, Experimentalist, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82204949 (to CLJ); Joint Program of Science and Technology Plan of Liaoning Province, No. 2023-MSLH-192 (to CLJ); General Program of Liaoning Provincial Department of Education, No. JYTMS20231813 (to CLJ); Basic Scientific Research Project Reserve for Universities, Liaoning Provincial Department of Education, No. 2024-JYTCB-013 (to CLJ); Open Fund of Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine, No. zyzx2008 (to CLJ)

摘要:


文题释义:
动物模型构建:动物模型是生物医学研究中建立的具有人类疾病模拟表现的动物实验对象和材料,使用动物模型是现代科技中一种便于认识生命科学客观规律的实验方法和手段,利用致病因素在动物身上模拟疾病发生发展即为动物模型构建,动物模型研究实质上是比较医学的应用科学。
脾虚型高脂血症动物模型:是病症结合动物模型,同时符合西医高脂血症和中医脾虚的特点,常用于阐释中医从脾脏象角度防治高脂血症的疗效、机制等研究。

背景:中医药防治脾虚高脂血症具有独特优势,基础研究中的脾虚高脂血症造模动物主要有大鼠、猪等,这对只能应用小鼠模型的医学研究而言具有局限性,亟待建立并评价脾虚高脂血症小鼠模型以支持中医药防治脾虚高脂血症的基础研究。
目的:建立脾虚高脂血症小鼠模型。
方法:采用随机数字表法将24只C57BL/6J小鼠随机分为正常组(n=12)和脾虚高脂组(n=12),正常组给予正常饲料喂养;脾虚高脂组采用饮食失常+劳倦内伤+高脂饲料喂养的方法制备脾虚高脂模型,前2周,单日游泳到耐力极限且仅喂食甘蓝,自由饮水,双日灌胃炼制猪油+高脂饲料喂养,2周后每天以高脂饲料喂养,持续至12周。高脂饲料喂养4,12周,检测小鼠体质量、饮食量、抓力、粪便含水量、小肠炭末推进率、血清D-木糖与胃泌素水平、脾脏指数与胸腺指数、血脂水平、全身脂肪质量、体脂率、肝脏脂质沉积。
结果与结论:①与正常组相比,脾虚高脂组小鼠高脂饲料喂养4,12周的体质量、粪便含水量、全身脂肪质量、体脂率、三酰甘油与总胆固醇水平均升高(P < 0.05),高脂饲料喂养4,12周的日饮食量、抓力、D-木糖水平均降低(P < 0.05),高脂饲料喂养4周的脾脏指数升高(P < 0.05),高脂饲料喂养12周的小肠炭末推进率、胃泌素水平、脾脏指数、胸腺指数均降低(P < 0.05),高脂饲料喂养12周的低密度脂蛋白胆固醇水平升高(P < 0.05);②肝脏油红O染色结果显示,脾虚高脂组高脂饲料喂养4周的脂质沉积稍多于正常组,高脂饲料喂养12周的脂质沉积明显多于正常组;③结果表明,采用饮食失常+劳倦内伤+高脂饲料喂养的方法可制备出稳定的脾虚高脂血症小鼠模型。
https://orcid.org/0009-0004-8138-5543(陈丽娟)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 脾虚, 高脂血症, 小鼠, 动物模型, 模型评价, 工程化组织构建

Abstract: BACKGROUND: Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia. In basic studies, models of spleen-deficiency and hyperlipidemia are commonly found in rats, pigs, and other animals. This has limitations for medical research that can only use mouse models. It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia.
OBJECTIVE: To establish a mouse model of spleen-deficiency hyperlipidemia.
METHODS: Totally 24 C57BL/6J mice were randomly divided into normal group (n=12) and spleen-deficiency hyperlipemia group (n=12). Mice in normal group were fed basic diet. Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model. In the first 2 weeks, the mice were forced to swim to their endurance limit on a single day and were only fed cabbage, with free access to water. They were also gavaged with refined lard + high-fat feed on two-day intervals. After 2 weeks, the mice were fed a high-fat diet every day and the diet continued until 12 weeks. The mice were fed with a high-fat diet for 4 and 12 weeks, and their body weight, food intake, gripping strength, fecal water content, small intestinal charcoal propulsion rate, serum D-xylose and gastrin levels, spleen index and thymus index, blood lipid level, total body fat mass, body fat percentage, and liver lipid deposition were tested.  
RESULTS AND CONCLUSION: (1) Compared with the normal group, the body weight, fecal water content, total body fat mass, body fat percentage, triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased (P < 0.05); the daily food intake, gripping force, and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased (P < 0.05); the spleen index of the mice fed with high-fat diet for 4 weeks was increased (P < 0.05); the small intestinal carbon propulsion rate, gastrin level, spleen index, and thymus index of the mice fed with high-fat diet for 12 weeks were decreased (P < 0.05); the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased (P < 0.05). (2) The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group, and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group. (3) The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders, exhaustion, and high-fat feeding. 

Key words: spleen deficiency, hyperlipidemia, mouse, animal model, model evaluation, engineered tissue construction

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