Study of the effect of CHOP signaling molecule in PPARα activation and inhibition with response to inflammation in mice with acute liver failure
10.3760/cma.j.cn501113-20200608-00298
- VernacularTitle:CHOP信号分子在PPARα激活抑制小鼠急性肝衰竭炎症反应中的作用研究
- Author:
Xiangying ZHANG
1
;
Ling XU
;
Yuan TIAN
;
Haiying JIN
;
Hongbo SHI
;
Feng REN
Author Information
1. 首都医科大学附属北京佑安医院 100069；北京市肝病研究所 100069
- Keywords:
Acute liver failure;
Inflammation;
Peroxisome proliferator-activated receptor alpha;
C/EBP homologous protein
- From:
Chinese Journal of Hepatology
2020;28(7):613-618
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism of action of peroxisome proliferator-activated receptor α (PPARα)-mediated CCAAT/enhancer binding protein homologous protein (CHOP) signaling molecule with response to inflammation in mice with acute liver failure.Methods:C57BL/6 mice were used as the research subjects, and D-galactose (D-GalN) combined with lipopolysaccharide (LPS) was injected intraperitoneally to establish a mouse model of acute liver failure. PPARα was activated by Wy-14643. CHOP expression was promoted by plasmids. Liver pathological changes and serum transaminases (ALT and AST) were detected in mice to evaluate liver function. The mRNA expression level of inflammatory factors in liver tissue was detected by real-time fluorescence quantitative PCR. LPS-stimulated macrophage was used to establish an inflammation model. PPARα and CHOP expression was inhibited by siRNA. The mRNA expression level of inflammatory factors in the cells was detected by real-time fluorescence quantitative PCR.Results:Promoted PPARα activation had inhibited liver hemorrhage and inflammation in mice with acute liver failure induced by D-GalN/LPS. In addition, the serum level of transaminases and genetic level of inflammatory factors in liver tissues were reduced ( P < 0.01). CHOP accelerated expression had reversed the hepatoprotective effect of PPARα activation, aggravated liver injury, and increased inflammatory factors expression ( P < 0.01). At the cellular level, the inhibition of PPARα activation had accelerated the increase of inflammatory factors ( P < 0.01), while the inhibition of CHOP activation had all over again decreased the inflammatory factors ( P < 0.01). Conclusion:PPARα and CHOP are important signaling molecules to regulate the inflammatory response in acute liver failure and liver injury. PPARα acceleration can down-regulate CHOP to inhibit inflammatory factors, which might play a protective role in mice with acute liver failure.
