EstablishingEstablishing a Modified Mouse Model for Post-prandial Hypertriglyceridemia

doi:10.3969/j.issn.1006-6179.2024.05.001

Laboratory Animal Science ›› 2024, Vol. 41 ›› Issue (5): 1-8.DOI: 10.3969/j.issn.1006-6179.2024.05.001

1. College of TCM, Beijing University of Chinese Medicine, Beijing 100020, China

2. National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100020,China

Received:2023-07-28 Online:2024-10-28 Published:2024-10-28

一种改良的餐后高三酰甘油血症小鼠模型的建立

1. 北京中医药大学中医学院,北京 100020 2. 北京中医药大学国家中医体质与治未病研究院,北京 100020

通讯作者: 李玲孺( 1986—) ,女,研究员,博士,研究方向为体质辨识与病证关系,E-mail:lilingru912@ 163. com。孙紫薇( 1990—) ,女,助理研究员,博士,研究方向为中医体质学,经典方剂的配伍与应用,E-mail:ziweisun@ 163. com。
作者简介:关媛媛( 1996—) ,女,在读硕士研究生,研究方向为体病相关与慢病防控研究,E-mail:20200931079@ bucm. edu. cn。
基金资助:
国家自然科学基金( 81874413) ;北京市科技新星计划( Z201100000820027) ;中华中医药学会“ 青年人才托举工程” ( CACM-

2018-QNRC2-C02) ;北京中医药大学科研创新团队项目( 2019-JYB-TD) ;中央高校基本科研业务费专项资金资助北京中医药

大学新教师启动基金( 2020-JYB-XJSJJ-004) ;中央级公益性科研院所基本科研业务费专项资金(YZ-202157)

Abstract

Abstract: Abstract: Objective The objective is to develop a better mouse model of post-prandial hypertriglyceridemia that closely resembles the dietary habits of humans. This model will serve as a reference for studying traditional Chinese medicine for preventing and treating post-prandial hypertriglyceridemia and related diseases. Additionally, it will aid in the development of healthcare products and drugs related to this condition. Method Thirty-two SPF-grade 5-week-old male ICR mice were randomly divided into 4 groups of 8 mice each after 1 week of adaptive feeding on standard diets, including the group of gavage 0. 9% NaCl solution, the group of gavage edible oil, the group of combined gavage edible oil and 30% fructose in water, and the group of intraperitoneal injection of P-407. According to the relevant references of the lipid tolerance experiment, it was decided to take the material after 120 min of gavage, and the relevant serological indexes ( TG, TC, HDL and LDL) were detected by

using a fully automatic biochemistry instrument. According to the experimental result, subsequent

experiments were conducted; 24 SPF grade 5-week-old male ICR mice were randomly divided into 12

blank groups and 12 model groups after being acclimatized to standard chow for 1 week. In the blank

group, 0. 7 mL of 0. 9% NaCl solution was given by gavage, and in the model group, 0. 5 mL of peanut

oil and 0. 2 mL of 30% fructose water were given by gavage. After 120 min of gavage, the material was

taken and the glycolipid-related biochemical indexes ( TG, TC, HDL, LDL, AST, ALT, GLU and ALP)

were detected by fully automatic biochemistry instrument; the levels of serum SOD and MDA were

detected by the superoxide dismutase ( SOD) and malondialdehyde ( MDA) kits to assess the level of

oxidative stress; the hepatic pathological conditions were observed by HE staining and oil red O staining;

the liver was observed by transmission electron microscopy. The liver pathology was observed by HE and

oil red O staining; mitochondrial morphology in hepatocytes was observed by transmission electron

microscopy. Result

The combined gavage of edible oil and fructose water was more consistent with the

mechanism of post-prandial lipid elevation in humans. It could significantly increase the TG level in mice

after meals. In the follow-up experiments, serum TG, LDL, GLU, ALT, AST and ALP were significantly

increased and HDL was significantly decreased in the model group. Serum SOD level was significantly

reduced and MDA level was significantly increased in the model group. HE staining of hepatocytes in the

model group showed slight structural changes, lipid droplet aggregation was seen in hepatic oil red O

staining, and the phenomenon of mitochondrial endoplasmic reticulum following lipid droplets in

hepatocytes was seen in transmission electron microscopy. Conclusion A modified postprandial hypertriglyceridemic mouse model can be successfully established by gavage with a combination of peanut oil and 30% fructose water, and this disorder of glycolipid metabolism may be related to oxidative stress and mitochondrial function.

Key words:

post-prandial hypertriglyceridemia, mouse model, lipid-lowering

摘要： 目的探索建立一种改良的餐后高三酰甘油血症的小鼠模型,以期更好地模拟人类饮食结构和习惯,为研究中医药防治餐后高三酰甘油血症及其相关疾病,以及相关保健品和药物的开发提供动物模型参考。方法将 32只 SPF 级 5 周龄雄性 ICR 小鼠经标准饲料适应性喂养 1周后随机分为灌胃 0. 9%氯化钠溶液组、灌胃食用油组、组合灌胃食用油和 30%果糖水组、腹腔注射 P-407 组,一共 4 组,每组 8 只。根据脂耐量实验的相关参考文献决定在灌胃 120min 后取材,并利用全自动生化仪检测相关血清学指标(TG、TC、HDL 和 LDL)。根据实验结果,进行后续实验;24 只 SPF 级 5 周龄雄性 ICR 小鼠经标准饲料适应性喂养 1周后随机分为空白组(12 只) 和模型组(12 只)。其中,空白组给予 0. 7 mL 的 0. 9%氯化钠溶液灌胃,模型组给予 0. 5mL 的花生油和 0. 2 mL30%果糖水灌胃。灌胃120min 后取材,并利用全自动生化仪检测糖脂相关生化指标( TG、TC、HDL、LDL、AST、ALT、GLU 和 ALP);超氧化物歧化酶(SOD)和丙二醛(MDA)试剂盒检测了血清 SOD、MDA 的含量以评估氧化应激水平;利用 HE 染色和油红O 染色观察肝病理情况;透射电镜观察肝细胞内线粒体形态。结果组合灌胃食用油和果糖水更符合人类餐后血脂升高的机制,可以显著升高餐后小鼠 TG 水平。在后续实验中,模型组小鼠相关生化指标血清 TG、LDL、GLU、ALT、AST、ALP 显著升高,HDL 显著下降。模型组小鼠血清 SOD 水平显著降低,MDA 水平显著升高。 HE 染色模型组肝细胞结构轻微改变,肝油红 O 染色可见脂滴聚集,透射电镜可见肝细胞内线粒体内质网与脂滴相随的现象。结论通过花生油和 30%果糖水组合灌胃,可以成功建立一种改良的餐后高三酰甘油小鼠模型,这种糖脂代谢紊乱可能与氧化应激和线粒体功能有关。

关键词:

餐后高三酰甘油血症, 小鼠模型, 降脂

CLC Number:

Q95-3

GUAN Yuanyuan , LIU Meiyi , WANG Liying , LI Mingrui , ZHENG Yi , LI Lingru , SUN Ziwei. EstablishingEstablishing a Modified Mouse Model for Post-prandial Hypertriglyceridemia[J]. Laboratory Animal Science, 2024, 41(5): 1-8.

关媛媛, 刘美怡, 王立英, 李明瑞, 郑艺, 李玲孺, 孙紫薇. 一种改良的餐后高三酰甘油血症小鼠模型的建立[J]. 实验动物科学, 2024, 41(5): 1-8.

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