Effect of inositol requiring enzyme 1-mediated endoplasmic reticulum stress in liver cell apoptosis of experimental fulminant hepatic failure and its significance
10.3760/cma.j.issn.1000-6680.2012.12.003
- VernacularTitle:需肌醇酶1介导的内质网应激在暴发性肝功能衰竭肝细胞凋亡中的作用及其意义
- Author:
Zhen ZHEN
;
Qing DIAO
;
Haiyan GE
;
Caiyan ZHAO
;
Junying ZHOU
- Publication Type:Journal Article
- Keywords:
Liver failure;
Apoptosis;
Endoplasmic reticulum stress;
Inositol;
Caspase-12
- From:
Chinese Journal of Infectious Diseases
2012;(12):716-720
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the role of inositol requiring enzyme 1 (IRE1)-mediated endoplasmic reticulum stress on hepatocyte apoptosis of experimental fulminant hepatic failure (FHF).Methods Thirty male depuratory Wistar rats were manufactured to be FHF model by peritoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS),and 30 rats were injected peritoneally with 0.9％ sodium chloride solution as controls.The apoptosis of liver cells was detected by flow cytometry.The protein and mRNA expressions of Caspase-12 and IRE1 in liver tissues were detected by immunohistochemistry and reverse transcriptation-polymerase chain reaction (RT-PCR).The independent samples were compared by Kruskal-Wallis H test.The comparison between two groups at the same time point was done by Mann-Whitney U test.The correlation analysis was done by rank correlation.Results The apoptotic rates of liver cells at 2,4,8 and 12 hours were increased over time in model group (x2 =25.475,P=0.01),which were higher than control group (U=0,P＜0.01).The expressions of Caspase-12 and IRE1 proteins in liver tissues were upregulated in model group,while the expressions were not detected in control group.The expressions of Caspase-12 and IRE1 mRNA in model group were also increased over time and peaked at 8 h,then gradually decreased; the differences among different time points were statistically significant (x2 =23.983,x2 =24.820; both P＜0.01),and all higher than control group (U=0,P＜0.01).IRE1 was positively correlated with both Caspase-12 and hepatocellular apoptotic rate (r=0.733 and 0.715,respectively;both P＜0.01).Caspase-12 was positively correlated with hepatocellular apoptotic rate (r=0.586,P＜0.01).Conclusions IRE1 mediated endoplasmic reticulum stress on hepatocyte apoptosis is closely related to the development of FHF.The earlier intervention on endoplasmic reticulum stress pathway,the more protective effect in liver failure.
