The role of glycogen synthase kinase-3 beta in the pathogenesis of liver ischemia reperfusion injury.
- VernacularTitle:糖原合成酶激酶-3β在肝脏热缺血再灌注损伤中的作用及其干预
- Author:
Feng REN
1
;
Hai-yan ZHANG
;
Zheng-fu PIAO
;
Su-jun ZHENG
;
Yu CHEN
;
Zhi-ming WU
;
Zhong-ping DUAN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Glycogen Synthase Kinase 3; metabolism; Glycogen Synthase Kinase 3 beta; Inflammation; metabolism; Liver; metabolism; pathology; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury; metabolism; pathology
- From: Chinese Journal of Hepatology 2011;19(7):547-551
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of the key intracellular signaling molecule glycogen synthase kinase-3 beta in the mechanism of liver ischemia reperfusion (IR).
METHODSC57BL/6 mice were subjected to 90 min warm liver cephalad lobe ischemia, followed by various length of reperfusion. Experiment groups included sham control group, liver IRI model group and glycogen synthase kinase-3 beta inhibitor-treated group (SB216763 in DMSO, 25 g/kg, i.p, 2 hour prior to the onset of liver ischemia). The expression of glycogen synthase kinase-3 beta protein was analysed by Western blotting. The serum ALT levels were determined to reflect the function of liver. The affected liver lobes were harvested for histology analysis. The inflammatory gene expression was detected by Quantitative PCR.
RESULTSBy western blot analysis, we found that ischemia itself activated glycogen synthase kinase-3 beta by a significant decrease of its phosphorylation. Glycogen synthase kinase-3 beta inhibitor SB216763-pretreatment ameliorated the liver damages significantly as compared to the controls (sALT: 2046+/-513 U/L vs 5809+/-1689 U/L, P = 0.0153), and suppressed the gene expressions of IL-12, TNFa, IL-1b and IL-6.
CONCLUSIONSThis study demonstrated that the ischemia process modulated liver innate immune activation via a GSK-3-dependent mechanism which favored the development of a pro-inflammation response and lead to liver tissue damages. GSK-3b may be a new therapeutic target to ameliorate liver IRI in transplant patients.