动物造模,暴发性肝衰竭 z-bio 2022-09-28 240

　　Objective To investigate the effect of prostaglandin e 1 (PGE1) on liver function in rats with fulminant liver failure (FHF) and its effect on eukaryotic translation initiation factor 2 α (eIF2 α) / Activates the regulation of the transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) pathway.

　　Methods Ninety male SPF SD rats were randomly divided into control group, model group, positive control group, low, medium and high dose PGE1 groups. Except for the control group, the FHF rat model was established by intraperitoneal injection of D-GalN LPS. The control group was intraperitoneally injected with the same amount of normal saline. Six hours after modeling, the positive control group and low, medium and high dose PGE1 groups were injected with hepatocyte growth promoting hormone 1.36 mg/kg via tail vein respectively, and PGE1 12.5, 25 and 37.5 μ G/kg, once a day, for 3 consecutive days, the control group and the model group were injected with the same amount of normal saline through the tail vein. The rats were killed 72 hours after modeling, and blood was collected from abdominal aorta to detect the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL); The liver tissues were dissected and the pathological changes of liver tissues were observed by hematoxylin eosin (HE) staining; Detection of eIF2 in liver tissues by real-time fluorescent quantitative PCR (qRT-PCR) and Western blot α/ ATF4/CHOP/Caspase-3 mRNA and protein, phosphorylated eIF2 α (p-eIF2 α) Protein level.

　　Results Compared with the control group, hepatocytes in the model group showed extensive degeneration and focal necrosis, central vein damage, serum ALT, AST, TBIL, and eIF2 in liver tissue α、 ATF4, CHOP, Caspase-3 mRNA and p-eIF2 α/ eIF2 α、 The levels of ATF4, CHOP and Caspase - 3 protein increased (P<0.05); Compared with the model group, the positive control group, low, medium and high dose PGE1 groups had lower liver cell damage, decreased the number of necrotic cells, serum ALT, AST, TBIL levels, and eIF2 in liver tissue α、 ATF4, CHOP, Caspase-3 mRNA and p-eIF2 α/ eIF2 α、 The levels of ATF4, CHOP and Caspase-3 protein decreased (P<0.05); With the increase of PGE1 dosage, the levels of ALT, AST, TBIL in serum and eIF2 in liver tissue of low, medium and high dose PGE1 groups α、 ATF4, CHOP, Caspase-3 mRNA and p-eIF2 α/ eIF2 α、 The levels of ATF4, CHOP and Caspase-3 protein decreased in a dose-dependent manner (P<0.05); Compared with the positive control group, the levels of ALT, AST, TBIL in serum and eIF2 in liver tissue of low and middle dose PGE1 groups α、 ATF4, CHOP, Caspase-3 mRNA and p-eIF2 α/ eIF2 α、 The levels of ATF4, CHOP and Caspase-3 protein were all increased (P<0. pge1="" tbil="" caspase-3="" mrna="" p="">0. 05).

　　Conclusion PGE1 may inhibit eIF2 α/ The expression of ATF4/CHOP pathway can reduce rat hepatocyte apoptosis and protect the liver, which may be a potential therapeutic drug for FHF.