IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制

祥蔚; 王晓东; 李政言; 谢斌; 甘立霞

doi:10.16016/j.1000-5404.201701092

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IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制

基础医学 | 更新时间：2026-01-09

- IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制
- IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice
- 第三军医大学学报 2017年39卷第16期页码：1599-1605
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81270482)
- DOI：10.16016/j.1000-5404.201701092
  中图分类号：
- 收稿：2017-01-11，
  
  纸质出版：2017-08-30
- 稿件说明：
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祥蔚, 王晓东, 李政言, 等. IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制[J]. 第三军医大学学报, 2017,39(16):1599-1605.

Wei XIANG, Xiaodong WANG, Zhengyan LI, et al. IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(16): 1599-1605.
祥蔚, 王晓东, 李政言, 等. IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制[J]. 第三军医大学学报, 2017,39(16):1599-1605. DOI： 10.16016/j.1000-5404.201701092.

Wei XIANG, Xiaodong WANG, Zhengyan LI, et al. IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(16): 1599-1605. DOI： 10.16016/j.1000-5404.201701092.

摘要

Abstract

Objective

To investigate the effect of interleukin 17A (IL-17A)deficiency on lipopolysaccharide(LPS)-induced liver injury in mice with long-term high fat diet feeding and explore the underlying mechanism.

Methods

C57BL/6 mice with IL-17A gene knockout (KO) and the wild-type (WT) littermates fed with high fat diet for 3 months were given an intraperitoneal injection of 4 mg/kg lipopolysaccharide (LPS). Plasma levels of alanine transaminase(ALT) and aspartate transaminase (AST) were detected to assess liver injury. Plasma TNF-α

IL-1β and IL-6 levels were determined to assess the severity of inflammation. Inflammatory cell infiltration in the liver and the impairment of hepatic cells were observed. The liver tissues from the WT and KO mice were subjected to transcriptomic analysis to study the effect of IL-17A deficiency on high-fat-diet-and LPS-induced liver injuries.

Results

High fat diet feeding and LPS challenge significantly decreased the plasma ALT and AST levels in IL-17A KO mice (

0.05). In the KO mice

the plasma levels of inflammatory cytokines and the number of infiltrating inflammatory cells in the liver were reduced significantly(

0.05). Transcriptomic analysis showed that 938 genes were down-regulated in the KO mice after LPS stimulation

among which the genes involved in oxidation reduction process(

0.01)

hydrogen peroxide metabolic process (

0.01)

and glutathione metabolic process (

0.01) showed the most significant decreases. Real-time PCR demonstrated that a panel of metabolic enzymes participated in hydrogen peroxide detoxification

such as CAT

GPX1

IDH1

IDH2 and ME1

which were highly expressed in the KO mice (

0.05). The levels of reactive oxygen species (ROS) were significantly decreased in the liver of KO mice (

0.05). TUNEL assay indicated that the number of apoptotic cells was significantly reduced in the liver of KO mice(

0.05).

Conclusion

IL-17A deficiency may alleviate LPS-induced acute inflammatory injury in fatty liver mice by reducing hepatic ROS accumulation.

关键词

Keywords

references

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