二氢杨梅素改善CDAHFD诱导小鼠NASH的作用及机制研究

职业与健康 ›› 2024, Vol. 40 ›› Issue (19): 2612-2618.

二氢杨梅素改善CDAHFD诱导小鼠NASH的作用及机制研究

冉莉, 姚宇, 候鹏飞, 糜漫天, 朱俊东

陆军军医大学（第三军医大学）军事预防医学系军队营养与食品安全研究中心,重庆市医学营养研究中心,重庆市营养与健康重点实验室,重庆 400038

收稿日期:2024-02-19 修回日期:2024-03-27 发布日期:2026-03-17
通信作者: 朱俊东,教授,E-mail：zjd2020_amu@163.com
作者简介:冉莉,女,高级实验师,主要从事营养与疾病研究工作。
基金资助:
国家自然科学基金（82003458）; 重庆市自然科学基金面上项目（cstc2020jcyj-msxmX0507）

Effect and mechanism of dihydromyricetin improving choline-deficient and L-amino acid-restricted high-fat diet-induced non-alcoholic steatohepatitis in mice

RAN Li, YAO Yu, HOU Pengfei, MI Mantian, ZHU Jundong

Research Center for Military Nutrition and Food Safety,Faculty of Military Preventive Medicine,Army Medical University（Third Military Medical University）,Chongqing Research Center for Medical Nutrition,Chongqing Key Laboratory of Nutrition and Health,Chongqing 400038,China

Received:2024-02-19 Revised:2024-03-27 Published:2026-03-17
Contact: ZHU Jundong,Professor,E-mail：zjd2020_amu@163.com

摘要/Abstract

摘要： 目的研究二氢杨梅素（dihydromyricetin,DHM）改善胆碱缺乏的L-氨基酸限定的高脂饮食（choline deficient L-amino acid restricted high-fat diet,CDAHFD）诱导小鼠非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）的作用及机制。方法采用CDAHFD喂养C57BL/6J小鼠4周建立NASH模型,24只雄性小鼠随机分为对照组（control group,CT）、模型组（CDAHFD）、二氢杨梅素干预组（DHM）。CT组喂养对照饲料,其余2组喂养CDAHFD饲料,DHM组每天以200 mg/kg·bw剂量的DHM灌胃,CT组和CDAHFD组用生理盐水灌胃,监测各组小鼠摄食量和体质量。干预4周后检测小鼠血清和肝组织中的生化指标,利用H&E、油红O、天狼星红染色观察肝组织形态学变化,qRT-PCR法检测肝脏炎症、脂质沉积和纤维化相关基因的表达水平。结果与CT组比较,CDAHFD组小鼠肝指数明显升高（P<0.05）,DHM干预后显著逆转CDAHFD诱导的血清谷氨酸转氨酶、天冬氨酸转氨酶水平,NAFLD活动度评分。肝脏三酰甘油、总胆固醇含量、肝组织中纤维化相关基因（Col1α1、Col3α1、Timp1）、炎症因子和趋化因子相关基因（Tnf-α、Cxcl2、Cxcl10、Mcp1 mRNA）表达以及肝组织中肿瘤坏死因子-α、白细胞介素1β蛋白水平升高（P<0.05）。相比CDAHFD组,DHM干预组肝脏组织中脂肪酸氧化相关基因Pparα mRNA表达,还原型谷胱甘肽和超氧化物歧化酶水平均显著升高（均P<0.05）,H&E染色、油红O染色、天狼星红染色结果显示,DHM干预组小鼠肝脏脂质沉积、胶原纤维沉积均显著改善。结论 DHM可改善CDAHFD诱导NASH模型小鼠的肝损伤、肝脏脂质沉积、纤维化水平,其机制可能与抗炎、抗氧化作用密切相关。

关键词: 非酒精性脂肪性肝炎, 二氢杨梅素, 肝损伤, 脂质沉积, 肝纤维化

Abstract: Objective To explore the effect and mechanism of dihydromyricetin（DHM） in improving nonalcoholic steatohepatitis （NASH） of mice induced by choline deficient L-amino acid restricted high-fat diet（CDAHFD）. Methods The NASH model was established by feeding C57BL/6J mice with CDAHFD for 4 weeks. Twenty-four male mice were randomly divided into three groups（CT,CDAHFD,and DHM）,the CT group was provided with the standard food,and other groups were fed with the CDAHFD diet. Mice in the DHM group were gavaged with 200 mg/kg·bw DHM daily. Mice in CT and CDAHFD groups were gavaged with normal saline. The food intake and body mass of mice were recorded. After 4 weeks of intervention,the biochemical indexes of serum and liver tissue were detected. To observe the histomorphologic changes of the liver,the HE,Oil red O,and Sirius red staining were performed. The relative mRNA expression levels of genes related to liver inflammation,lipid deposition,and fibrosis were determined by qRT-PCR. Results Compared with the CT group,the liver index of mice in the CDAHFD group was significantly increased（P<0.05）,and DHM intervention significantly reversed the serum alanine aminotransferase and aspartate aminotransferase levels induced by CDAHFD,as well as the NAFLD activity score. The content of liver triglyceride and total cholesterol content,the expression of fibrosis related genes in liver tissue（Co1α1,Col3α1,Timp1）,inflammatory and chemokine related genes（Tnf-α,Cxcl2,Cxcl10,Mcp1mRNA）,and the level of tumor necrosis factor-α,Interleukin-1 β protein in liver tissue increased（P<0.05）. Compared with CDAHFD group,DHM also increased the Pparα mRNA expression and glutathione as well as the superoxide dismutase content in liver（P<0.05）. The results of H&E staining,oil red O staining and Sirius red staining also showed that liver lipid deposition and collagen fiber deposition were significantly improved in DHM intervention group. Conclusion DHM can improve the liver injury,hepatic steatosis and fibrosis in CDAHFD induced NASH of mice. As for the mechanism,anti-inflammation and anti-oxidant maybe play a key role in the process.

Key words: Non-alcoholic steatohepatitis, Dihydromyricetin, Liver injury, Lipid deposition, Fibrosis

中图分类号:

R151.2

冉莉, 姚宇, 候鹏飞, 糜漫天, 朱俊东. 二氢杨梅素改善CDAHFD诱导小鼠NASH的作用及机制研究. [J]职业与健康, 2024, 40(19): 2612-2618.

RAN Li, YAO Yu, HOU Pengfei, MI Mantian, ZHU Jundong. Effect and mechanism of dihydromyricetin improving choline-deficient and L-amino acid-restricted high-fat diet-induced non-alcoholic steatohepatitis in mice. [J]OCCUPATION AND HEALTH, 2024, 40(19): 2612-2618.

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