动物造模,暴发性肝衰竭 z-bio 2021-12-31 461

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

　　Methods Ninety SPF SD male rats were divided into control group, model group, positive control group, low, medium, and high dose PGE1 groups according to the random number table method. Except for the control group, all rats in the other groups were injected intraperitoneally with D- The FHF rat model was established by the method of galactosamine (D-GalN)-E. coli endotoxin lipopolysaccharide (LPS), and the control group was intraperitoneally injected with the same amount of normal saline. Six hours after modeling, the positive control group and the low, medium, and high-dose PGE1 groups were injected with hepatocyte growth-promoting factor 1.36 mg/kg, PGE1 12.5, 25, and 37.5 μg/kg, 1 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, blood was collected from the abdominal aorta, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels were detected; liver tissues were dissected The hematoxylin-eosin (HE) staining method was used to observe the pathological changes of the liver tissue of each group of rats; real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting (Western blot) were used to detect eIF2α/ ATF4 / in liver tissues. 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, damage to the central vein, serum ALT, AST, TBIL, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/ The protein levels of eIF2α, ATF4, CHOP, and Caspase-3 were increased (P<0.05); compared with the model group, liver cell damage in the positive control group, low, medium, and high-dose PGE1 groups was reduced, and the number of necrotic cells Decrease, serum ALT, AST, TBIL levels, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/ eIF2α, ATF4, CHOP, and Caspase-3 protein levels in liver tissue decreased (P<0.05); and With the increase in the dose of PGE1, serum ALT, AST, TBIL levels in low, medium, and high dose PGE1 groups, eIF2α, ATF4, CHOP, Caspase-3 mRNA and p-eIF2α/ eIF2α, ATF4, CHOP, Caspase- in liver tissues 3 Protein levels decreased sequentially (P<0.05), in a dose-dependent manner; compared with the positive control group, serum ALT, AST, TBIL levels in the low and medium dose PGE1 groups, eIF2α, ATF4, CHOP, Caspase- 3 mRNA and p-eIF2α/ eIF2α, ATF4, CHOP, Caspase-3 protein levels increased (P<0. pge1="" tbil="" caspase-3="" mrna="" p="">0 . 05).

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