Research On Genes And Proteins Related To Acute Hepatic Failure

Acute hepatic failure(AHF)is a kind of liver disease with high mortality rate caused by a variety of factors and seriously threatens people's health.It severely damages the liver cell and leads to dysfunction of synthesis,detoxification and biotransformation of the liver.AHF happens often accompanied by multiple organ failure,coagulation disorders,hepatic encephalopathy,secondary infection,hemodynamic disorders and metabolic complications.It is not fully understood about the pathogenesis and molecular mechanism of AHF because of the complexity due to numerous factors.So,current treatment to AHF is mainly focused on the comprehensive treatment due to the lack of effective control measures.For this reason,AHF has been one of the most challenging diseases on clinical medicine.In this paper,we successfully constructed the AHF rat model and tested the modelling effect by detecting the enzymatic activity of serum alanine transaminase(ALT)and aspartate aminotransferase(AST),and counting the coefficient of liver and observing of frozen sections under microscopic.We detected gene expression profile and found 4819 genes associated with AHF utilizing the Rat Genome 230 2.0 Gene Chip(RGC).We uploaded the data to Ingenuity Pathway Analysis(IPA)and found that IL-1,IL-6 and IL-8 signaling pathway signaling activated and p53,ATM and AMPK signaling pathway decreased.Cell survival,proliferation and differentiation activated,at the same time,the apoptosis of T and B lymphocytes decreased.After the analysis of the gene expression related to AHF we predict that IL-1??IL-1R1??MAPK8?FOS/JUN and/or TNF??TNFRSF1A/B??Caspases pathway regulate apoptosis at injury and progressing stage,inflammatory factors regulate apoptosis by NF-?B pathway at progressing stage,TP53 inhibits apoptosis at progressing stage,apoptotic is i nhibited at recovery stage due to the down-regulation of Caspase3 and the injury was repaired by proliferation at progressing and recovery stage due to the up-regulation of PCAN.Therefore,we speculate that IL-1R1,TNFRSF1 A / B,Caspase3,TP53,PCNA and NF-?B play a critical role in the acute liver failure which was induced by CCl4.We explored the gene therapy on AHF mice applying hydrodynamics-based transgene(HDT)created by our laboratory and successfully constructed the AHF mice model and verified the reliability by testing ALT and AST in serum and observing of frozen sections under microscopic.We took different injection-methods to explore the effect of constructing the AHF model.Specifically,we choose two different injection:normal saline injection and pEGFP-C1 injection,and made intragastric administration and injection with different sequence and time lag.At last,We found that there was no significant difference between two methods at 6h after gavage and modeling.All these lay a foundation for gene therapy on AHF.In summary,we discussed and analyzed the mechanism of AHF and studied the optimal injection conditions of target gene into AHF model via HDT technology which lay a foundation for further research and treatment.