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The Expression Of Related Gene In Acute Hepatic And Renal Ischemia-reperfusion Injury And The Effects Of Remote Ischemic Preconditioning

Posted on:2024-01-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y MaFull Text:PDF
GTID:1524307085474244Subject:Anesthesiology
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Objective: The differential expression of genes after IRI in liver and kidney was analyzed to determine related Hub genes and their possible functions and markers;at the same time,in the aspect of Hub gene function,we further analyzed and compared the function of liver,kidney,inflammatory factors and the expression of IRI-related Hub genes in kidney after liver IR with or without RIPC,and analyzed its possible mechanism.Methods: 1)the gene profiles related to IRI in liver and kidney were selected from the gene pool,and the Hub genes related to IRI in liver and kidney and their functions and possible markers were determined by analysis.2)to observe and compare the function of liver and kidney,the level of inflammatory factors and the expression of IRI-related Hub gene in kidney after liver IR with or without RIPC.Results: 1)in the differential expression analysis of liver IRI gene,283 common genes were found to be related to liver IR before and after orthotopic liver transplantation(OLT).The main biological functions of these genes were positive regulation of cell death,apoptosis signal pathway,vascular development and so on.IL6,CCL2 and CXCL8 may be involved in the process of ischemia-reperfusion.By further comparing the gene expression of IRI+ and IRI-patients during orthotopic liver transplantation,32 common genes related to IRI were found.Ten Hub genes(AGBL4,Rp4_781K5,PTH2 R,RP11_701P16,ITGA2,HKDC1,NARF_IT1,CILP2,IL4I1,MT1P3)may have the ability to distinguish IRI+ from IRI-.The pathway of these genes is related to inflammation and metabolism,and the expression of AGBL4,CILP2 and IL4I1 is up-regulated in liver IRI patients.2)in the differential analysis of renal IRI gene expression,through the analysis of renal IRI related genes,it was found that Mmp9,Timp1,Spp1,CCL2,Serpine1 and CD44 may be Hub genes of renal IRI.The pathway of these genes is related to inflammation,apoptosis and renin angiogenesis system,in which Spp1,CCL2,Serpine1 and CD44 are regulated by DEmi Rs.3)RIPC was performed in patients with partial hepatectomy.Compared with the control group,there was no difference in the levels of serum ALT,AST,SCr,IL-6,CRP and PCT between the two groups at 24 h,48h and 72 h after operation.24 hours after operation,Mmp9,Timp1,Spp1,CCL2,Serpine1 and CD44 were all significantly underexpressed in RIPC patients compared to controls.Conclusion: The expression of AGBL4,CILP2 and IL4I1 is upexpressed in patients with liver IRI,and the pathway of these genes is related to inflammation and metabolism.Mmp9,Timp1,Spp1,CCL2,Serpine1 and CD44 in patients with renal IRI may be related to renal IRI.The pathway of these genes is related to inflammation,apoptosis and renin angiogenesis.Spp1,CCL2,Serpine1 and CD44 are regulated by DEmi Rs,suggesting that intervention of inflammatory balance may be beneficial to the protection of cellular function of renal IRI.In this study,it was not found that RIPC could affect liver function,renal function and the level of inflammatory factors within 72 hours after hepatectomy,but Mmp9,Timp1,Spp1,Serpine1,Ccl2 and Cd44 underexpressed in RIPC group at 24 hours after operation.The effect of RIPC on liver may not be produced through inflammatory channels.Although there are changes in the expression of IRI-related Hub gene in kidney after liver IR,there is no difference in functional level.The effect and mechanism of RIPC to IRI on liver and kidney needs further study.
Keywords/Search Tags:Ischemia-reperfusion injury, Differentially expressed genes, Remote ischemic preconditioning, Organ protection
PDF Full Text Request
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