二氢杨梅素对代谢相关脂肪性肝病小鼠结肠黏膜屏障功能改善作用研究

蒋玲; 李鹏飞; 候鹏飞; 周杰; 董妞; 张乾勇; 易龙; 糜漫天

doi:10.16016/j.2097-0927.202206187

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二氢杨梅素对代谢相关脂肪性肝病小鼠结肠黏膜屏障功能改善作用研究

基础医学 | 更新时间：2026-01-09

- 二氢杨梅素对代谢相关脂肪性肝病小鼠结肠黏膜屏障功能改善作用研究
- Dihydromyricetin improves colonic mucosal barrier function in mice with metabolism-associated fatty liver disease
- 陆军军医大学学报 2023年45卷第2期页码：146-154
- 作者机构：
  
  400038 重庆，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，重庆市营养与食品安全重点实验室
- 作者简介：
  
  [易龙, E-mail: longgyin8341@hotmail.com YI Long, E-mail: longgyin8341@hotmail.com
- 基金信息：
  
  国家自然科学基金面上项目(81872625);国家自然科学基金面上项目(82173505)
- DOI：10.16016/j.2097-0927.202206187
  中图分类号： R285.5;R333.3;R575.5
- 收稿：2022-06-29，
  
  修回：2022-08-18，
  
  纸质出版：2023-01-30
- 稿件说明：
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蒋玲, 李鹏飞, 候鹏飞, 等. 二氢杨梅素对代谢相关脂肪性肝病小鼠结肠黏膜屏障功能改善作用研究[J]. 陆军军医大学学报, 2023,45(2):146-154.

Ling JIANG, Pengfei LI, Pengfei HOU, et al. Dihydromyricetin improves colonic mucosal barrier function in mice with metabolism-associated fatty liver disease[J]. Journal of Army Medical University, 2023, 45(2): 146-154.
蒋玲, 李鹏飞, 候鹏飞, 等. 二氢杨梅素对代谢相关脂肪性肝病小鼠结肠黏膜屏障功能改善作用研究[J]. 陆军军医大学学报, 2023,45(2):146-154. DOI： 10.16016/j.2097-0927.202206187.

Ling JIANG, Pengfei LI, Pengfei HOU, et al. Dihydromyricetin improves colonic mucosal barrier function in mice with metabolism-associated fatty liver disease[J]. Journal of Army Medical University, 2023, 45(2): 146-154. DOI： 10.16016/j.2097-0927.202206187.

摘要

目的

研究二氢杨梅素(dihydromyricetin

DHM)对代谢相关脂肪性肝病(metabolic-associated fatty liver disease

MAFLD)的改善作用

并揭示其调节肠黏膜屏障功能的作用机制。

方法

32只雄性C57BL/6J小鼠随机分为4组(

=8): CON (对照

脂肪供能比为10%饮食)组、高脂饮食(HFD

脂肪供能比为45%)组、HFD+DHM组(添加质量比0.6% DHM的高脂饲料)和DHM组(添加质量比0.6% DHM的对照饲料)

干预12周。每周测量小鼠体质量、摄食量; 处死前进行空腹血糖、葡萄糖耐量和肠道通透性检测; 试剂盒检测血清生化指标、脂多糖(LPS); 肝组织进行油红O染色和HE染色

观察组织病理学变化; RT-qPCR和Western blot法检测肠上皮紧密连接蛋白、抗菌肽及肝脏炎症因子表达水平; 流式细胞术检测结肠3型固有淋巴样细胞(group 3 innate lymphoid cells

ILC3)比例以及IL-22表达水平。

结果

与CON组比较

HFD组小鼠体质量增加

糖耐量受损

血清总胆固醇、甘油三酯、谷丙转氨酶、谷草转氨酶升高

肝脏脂质沉积和炎性因子

-1

、

-6、

TNF

mRNA表达水平升高

肠道通透性和血清LPS增加

肠黏膜紧密连接蛋白

-1、

Occludin

及抗菌肽

Reg

Ⅲ

、

Reg

Ⅲ

表达水平降低

结肠ILC3及IL-22

ILC3比例降低(

0.05)。与HFD组比较

HFD+DHM组糖耐量受损明显改善

肝脏脂质沉积和炎性因子表达减少

血清LPS水平降低

肠紧密连接蛋白和抗菌肽表达水平增加

肠道通透性减少

结肠ILC3和IL-22

ILC3比例增加(

0.05)。

结论

DHM可能通过改善肠黏膜屏障功能减少肝脏脂质堆积和炎症反应

改善MAFLD疾病进程。

Abstract

Objective

To investigate the ameliorative effects of dihydromyricetin (DHM) on metabolism-associated fatty liver disease (MAFLD)

and to reveal the mechanism of its regulation of intestinal mucosal barrier function.

Methods

Thirty-two male C57BL/6J mice were randomly divided into 4 groups (

=8): CON (control diet

with 10% fat) group

HFD (high-fat diet

with 45% fat) group

HFD+DHM (high-fat diet+0.6% DHM) group

and DHM (control diet+0.6% DHM) gro

up.All the subjects were intervened for 12 weeks

the body weight and food consumption of mice were measured weekly.Fasting blood glucose

glucose tolerance and intestinal permeability were tested before sacrifice.Serum levels of biochemical indexes and lipopolysaccharide (LPS) were detected with corresponding kits.The liver tissues were stained with HE and oil red O staining

respectively

and the histopathological changes were observed.Moreover

RT-qPCR and Western blotting were used to measure the expression levels of intestinal epithelial tight junction proteins

antimicrobial peptides and liver inflammatory factors.Flow cytometry was adopted to determine the proportion of group 3 innate lymphoid cells (ILC3) and the level of IL-22 in the colon.

Results

As compared with the CON group

the HFD group presented increased body weight

impaired glucose tolerance

as well as elevated serum total cholesterol

triglyceride

alanine transaminase and aspartate transaminase.HFD also led to liver lipid deposition and higher mRNA levels of

-1

-6 and

TNF

in the liver.The intestinal permeability and serum LPS were increased

whereas the expression levels of tight junction proteins

-1 and

Occludin

and antimicrobial peptides

Reg

Ⅲ

and

Reg

Ⅲ

in the intestinal mucosa were decreased

and the proportions of ILC3 and IL-22

ILC3 in the colon were declined (

0.05).In the HFD+DHM group

the impaired glucose tolerance was significantly improved

the hepatic lipid deposition and the expression of inflammatory factors were reduced

so was the serum LPS level.DHM also upregulated the levels of intestinal tight junction proteins and antimicrobial peptides

and ameliorated the intestinal permeability.Furthermore

the colonic ILC3 and IL-22

ILC3 ratios were increased b

y DHM treatment as well (

0.05).

Conclusion

DHM may ameliorate the progression of MAFLD by improving intestinal barrier function to reduce lipid accumulation and inflammatory responses in the liver.

关键词

Keywords

references

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