Study on the mechanism of PPAR-γ dependent immunological idiosyncrasy liver injury induced by Polygonum multiflorum
10.16438/j.0513-4870.2016-0774
- VernacularTitle:PPAR-γ依赖的何首乌免疫性特异质肝损伤机制研究
- Author:
Lan-zhi HE
1
;
Ping YIN
1
;
Ya-kun MENG
1
;
Zhen-fang ZHANG
1
;
Hui-min LIU
1
;
He-rong CUI
1
;
Hao-tian NI
1
;
Jia-bo WANG
1
;
Xiao-he XIAO
2
;
Zhao-fang BAI
1
Author Information
1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
2. Integrative Medical Center for Liver Diseases, 302 Military Hospital, Beijing 100039, China
- Publication Type:SPECIAL REPORTS
- Keywords:
Polygonum multiflorum;
idiosyncratic hepatotoxicity;
PPAR-γ agonist;
NF-κB p65
- From:
Acta Pharmaceutica Sinica
2017;52(7):1027-1032
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.
