动物造模,暴发性肝衰竭 z-bio 2022-06-20 312

　　Objective To investigate the effect of alprostadil (PGE1) on liver function in rats with fulminant liver failure (FHF), and to investigate its effect on eukaryotic translation initiation factor 2α (eIF2α) / activating transcription factor 4 (ATF4) / C/ EBP Regulation of the homologous protein (CHOP) pathway.

　　Methods Ninety SPF SD male rats were divided into control group, model group, positive control group, low-dose, medium-dose and high-dose PGE1 groups according to random number table method. The FHF rat model was established by the method of galactosamine (D-GalN)-Escherichia coli endotoxin lipopolysaccharide (LPS), and the control group was intraperitoneally injected with the same amount of normal saline. 6 hours after modeling, the positive control group and low-dose, medium-dose and high-dose PGE1 groups were injected with hepatocyte growth-promoting hormone 1.36 mg/kg and PGE1 12.5, 25, 37.5 μg/kg, 1 per day, respectively. 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 sacrificed 72 hours after modeling, and blood was collected from the abdominal aorta to detect the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue in each group; real-time fluorescence quantitative PCR (qRT-PCR) and Western blot were used to detect eIF2α/ATF4/in liver tissue. CHOP/Caspase-3 (Caspase-3) mRNA and protein, phosphorylated-eIF2α (p-eIF2α) protein levels.

　　Results Compared with the control group, the model group had extensive degeneration of liver cells with focal necrosis, central vein damage, serum ALT, AST, TBIL, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/ The protein levels of eIF2α, ATF4, CHOP and Caspase-3 were all increased (P<0.05); compared with the model group, the damage of hepatocytes in the positive control group, low, medium and high doses of PGE1 groups decreased, and the number of necrotic cells decreased. decreased, serum ALT, AST, TBIL levels, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/eIF2α, ATF4, CHOP, Caspase-3 protein levels in liver tissue decreased (P<0.05); With the increase of PGE1 dose, serum ALT, AST, TBIL levels, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/eIF2α, ATF4, CHOP, Caspase-3 mRNA in liver tissue in low, medium and high dose PGE1 groups were significantly increased. 3. The protein levels decreased sequentially (P<0.05) in a dose-dependent manner; compared with the positive control group, the serum ALT, AST and TBIL levels in the low and middle dose PGE1 groups, eIF2α, ATF4, CHOP, Caspase- 3 mRNA and p-eIF2α/eIF2α, ATF4, CHOP, Caspase-3 protein levels were increased (P<0. pge1="" tbil="" caspase-3="" mrna="" p="">0 .05).

　　Conclusion PGE1 may inhibit the expression of eIF2α/ATF4/CHOP pathway, reduce the apoptosis of rat hepatocytes, and achieve the effect of protecting the liver. It may be a potential therapeutic drug for FHF.