Effect of inositol requiring enzyme 1-mediated endoplasmic reticulum stress in liver cell apoptosis of experimental fulminant hepatic failure and its significance / 中华传染病杂志

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.