Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice

被引：90

作者：

Liu, Jing ^{[1
]}

Zhuang, Zhen-jie ^{[2
]}

Bian, Dong-xue ^{[1
]}

Ma, Xiao-jie ^{[1
]}

Xun, Yun-hao ^{[3
]}

Yang, Wen-jun ^{[4
]}

Luo, Yan ^{[2
]}

Liu, Yin-lan ^{[2
]}

Jia, Ling ^{[1
]}

Wang, Yan ^{[5
]}

Zhu, Ming-li ^{[3
]}

Ye, De-wei ^{[6
]}

Zhou, Gang ^{[7
]}

Lou, Guo-qiang ^{[2
]}

Shi, Jun-ping ^{[2
]}

机构：

[1] Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou, Zhejiang, Peoples R China

[2] Hangzhou Normal Univ, Ctr Translat Med, Affiliated Hosp, Hangzhou 310015, Zhejiang, Peoples R China

[3] Xixi Hosp Hangzhou, Dept Liver Dis, Hangzhou, Zhejiang, Peoples R China

[4] Hangzhou Normal Univ, Dept Pathol, Affiliated Hosp, Hangzhou 310015, Zhejiang, Peoples R China

[5] Dalian Univ Med, Dalian, Peoples R China

[6] Univ Hong Kong, Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China

[7] Hangzhou Normal Univ, Dept Gastroenterol, Affiliated Hosp, Hangzhou 310015, Zhejiang, Peoples R China

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2014年 / 41卷 / 07期

基金：

中国国家自然科学基金;

关键词：

mice; non-alcoholic fatty liver disease; toll -like receptor 4; TOTAL PARENTERAL-NUTRITION; HEPATIC STEATOSIS; ACTIVIN-A; INNATE IMMUNITY; BINDING-PROTEIN; KUPFFER CELLS; STEATOHEPATITIS; LIPOPOLYSACCHARIDE; ACTIVATION; FIBROSIS;

D O I：

10.1111/1440-1681.12241

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut)) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.

引用

页码：482 / 488

页数：7

共 29 条

[1]

Nonalcoholic fatty liver disease [J].