Affiliation:
1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023, China
Abstract
Background:
CCl4 Acute Liver Injury (ALI) is a classical model for experimental research.
However, there are few reports involved in the fundamental research of CCl4-induced ALI.
Ligustri Lucidi Fructus (LLF) and its prescription have been used to treat hepatitis illness clinically.
LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of . function
has not yet been fully clarified.
Objective:
To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of
active Total Glycosides (TG) from LLF on ALI of mice4, including histopathological survey and
proteomic changes of liver tissues, and delineate the possible underlying mechanism.
Methods:
CCl4 was used to produce the ALI mice model. The model mice were intragastrically administrated
with TG and the liver histopathological changes of mice were examined. At the end of
the test, mice liver samples were collected, and after protein denaturation, reduction, desalination
and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology.
The data was processed by Maxquant software. The differentially-expressed proteins were
screened and identified, and their biological information was also analyzed based on GO and
KEGG analysis. Key protein expression was validated by Western blot analysis.
Results:
A total of 705 differentially-expressed proteins were identified in the normal, model and
administration groups. 9 significant differential proteins were focused based on the analysis. Liver
protein expression changes of CCl4-induced ALI mice were mainly involved in several important
signaling channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway.
TG has an anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1
and autophagy pathways.
Conclusion:
CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-
dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfering
with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose
and lipid, and causing hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression
level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance,
thus promoting autophagy and resistance to liver damage.
Funder
Programs Foundation of Ministry of Education of China
Publisher
Bentham Science Publishers Ltd.
Subject
Molecular Biology,Biochemistry