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The Impact Of Ciclosporin A On Mitochondria Function And Ischemical Reperfusion Injury In Rats After Liver Autotransplantation

Posted on:2009-05-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y M LiFull Text:PDF
GTID:1114360245982331Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective Liver possesses powerful regeneration capacity,the regulatory process of liver regeneration is extremely complex and multiple factors.Partial hepatectomy(70%)already becomes most frequently method to manufacture model of liver regeneration.Puzzle in excision of liver tumor is warm ischemia time limited and anatomy reveal difficulty,it is a fine alternative to solve the puzzle by liver transplantation technique,such as remnant liver reimplant after PH in situ hypothermy infuse,semi-ex vivo,ex vivo.There is relation between possible mechanism of apoptosis in liver regeneration and regulatory mechanism of permeability transformation in mitochondrium,it is unavoidable of ischemia reperfusion injury in organ transplantation.This study was designed to investigate the timeframe of liver regeneration, verificate the relation between apoptosis and permeability transformation in mitochondrium in liver regeneration,analyze protection in liver ischemia reperfusion injury by CsA preconditioning in rats.Methods First of all,the model of 70%partial hepatectomy and liver autotransplantation after 70%partial hepatectomy in situ hypothermy infuse were performed by Higgin method.The timeframe of liver regeneration was reflected by mensuration of liver regeneration degree and liver weight accrementition rate and detect expression of PCNA and Ki-67.Liver tissues were collected to detect apoptosis and the expression of cytC,Bax,Bcl-2 and Caspase-3,and the expression of TNF-a,ICAM-1,HO-1 and iNOS in liver ischemia reperfusion injury by CsA preconditioning in rats.Results 1 In formal operations,the anhepatic time was 2~5 min(3.14±1.56 min)and the successful rate was 100%after the liver grafts undergoing 0.5~1 min of warm ischemia and 1~4min of cold ischemia.2 The weights of livers in two groups reached about 50%on day 3 postoperation and about 100%on day 7 postoperation.The expression of PCNA and Ki-67 were obviously heighten,but compared with 70%partial hepatectomy(PH),the peak time of PCNA-LI and Ki-67-LI was also delayed 24 hours in liver autotransplantation after 70%partial hepatectomy in situ hypothermy infuse.3 CsA is specific inhibitor of MPTP,The expression of protein of cytC of liver tissue in PC group were lower than NS group significantly 2h and 6h after reperfusion(P<0.05).The expression of mRNA and protein of Caspase-3 in PC group were lower than NS group significantly 6h and 24h after reperfusion(P<0.05).There were not significant difference of the expression of protein of Bcl-2 and Bax between two groups.4 The expression of protein of TNF-a and ICAM-1 in PC group were lower than NS group significantly 2h and 6h after reperfusion(P<0.05), The expression of mRNA of TNF-a and ICAM-1 in PC group were lower than NS group significantly 6h after reperfusion(P<0.05).The expression of protein of iNOS in PC group were lower than NS group significantly 6h after reperfusion(P<0.05).The expression of protein of HO-1 in PC group were higher than NS group significantly 6h after reperfusion(P<0.05).Conclusion1 The rat model of 70%partial hepatectomy and liver autotransplantation after 70%partial hepatectomy in situ hypothermy infuse performed by Higgin method is reliable to study the basic and clinical problems of liver transplantation.2 Liver possesses powerful regeneration capacity,the recovery of liver function regard as important,but no recover morphous absolutely.They are significance indexes of PCNA and Ki-67 to reflect cell multiplication in liver.3CsA can inhibit the open of MPTP to abate release of apoptosis medium,such as cytC,and inhibit cascade reaction of caspase to inhibit apoptosis.CsA not only cann't promote the expression of Bcl-2,but also cann't restrain the expression of Bax.4 There is relationship between abatement of liver I/R injury and inhibition of the expression of TNF-a and ICAM-1 by CsA preconditioning.CsA can promote the expression of heat shock protein(HO-1)and inhibit the expression of iNOS to attenuate liver I/R injury efficiently.
Keywords/Search Tags:liver autotransplantation, liver regeneration ciclosporinA, ischemical reperfiision injury, mitochondrium
PDF Full Text Request
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