| BackgroundIschemic preconditioning (IP) refers to the increased tissue resistance to ischemia reperfusion injury (IRI) that can be induced by the pre-exposure to one or more brief periods of hypoxia followed by reoxygenation. There are two distinct phases of IP, the early and the delayed preconditioning. The heat stress response is associated with the induction of heat shock protein (HSP). The heat preconditioning contributes to the protection in the late phase of IRI in rat liver. Investigating the protective effects of liver preconditioning plays an important role in the liver transplantation and other liver operations. But the mechanism of the preconditioning is not clarified clearly. ObjectivesWe evaluated the protective effects of Ischemia Preconditioning and the Heating Preconditioning for ischemia reperfusion injury in an in vivo rat model of liver transplantation. Administration of N-Nitro-L-arginine Methyl Ester (L-NAME) has also been used during these processes to study the protection to liver by IP.Part I Protective effect of preconditioning on rat donor livers in arat model of Ischemic Reperfusion Injury.Objectives :Established several preconditioning rat models for liverpreserving.Methods: A total of 48 male SD rats were randomly assigned to 6 groups,each including 8 rats. 1. hepatic IP group, 2. partial hepatic IP group,3. spleen IP group, 4. heat preconditioning group, 5. heatpreconditioning + IP group, 6. control group. The extent of the hepaticinjury was estimated with the level of ALT in perfusion solution of liverand the morphology changes.Results: The levels of ALT in the first 5 groups were lower than in thecontrol group (P<0.05) . Among the first 5 groups, the level of ALT in the group that is treated with ischemia and heat is higher than the others dramatically (P<0. 05) .There were similar results in liver pathology. Conclusion: Protective effects of IP and heating preconditioning are beneficial to the hepatic IRI. But the combination of these two methods seems to attenuate the protection. The spleen IP can also protect the rat liver from IRI.Part II Production of in vivo rat model of liver transplantationObjectives foundation of rat model of orthotopic liver transplantationand the simplified rat simulaton model. Make the comparision of these twomethods.Methods: After a lot of practice and investigations, be proficient inthe modified cuff techniques. A simplified rat simulation model ofothotopic liver transplantion has been founded. Compare the surgicalinterventions, survival rate and the serum chemistry between these tworat models.Results: The foundation of rat model by the techniques of modified cuffneeds a lot of exercises, while the simplified rat simulation model ofothotopic liver transplantion seems more applicable. The easy handlingoperation, increased survival rate and decreased serum aminotransferasewere founded at the latter model.Conclusion: The simplified rat simulation model of othotopic livertransplantion are more applicable in the experiment than modified cufftechniques. For it has less interference factors.Part III Comparision of protective effects of different liver preconditioning in liver transplantation.Objectives :Compare different liver preconditioning methods on the rat model of simulation model of othotopic liver transplantaton. . Methods: A total of 50 male SD rats were randomly allocated into 5 groups. 1. liver IP group. 2. spleen IP. 3. heat preconditioning. 4. heat preconditioning+IP. 5. Control group. After the rat othotopic liver transplantation, the bile flow, level of serum transaminase and themorphological changes of the liver were measured.Results: The outcome of bile flow, levels of serum ALT, AST level and the morphology of liver is much better in the IP group and the heat preconditioning group than the control group (P<0.05) . While the combination of these two methods seems to attenuate the protection as demonstrated by serum ALT level and the liver histology (P<0. 05) . The spleen IP also show the protection against IRI (P<0. 05) . Conclusion: Protective effects of IP and heating preconditioning are beneficial to the hepatic IRI. But the combination of these two methods seems to attenuate the protection. The spleen IP can also protect the rat liver from IRI.Part IV Effect of administration of L-NAME, the NOS inhibitor, in theliver preconditioning in rat liver transplanation.Objectives : Effect of administration of L-NAME, the NOS inhibitor, inthe liver preconditioning on the donor rat livers.Methods: A total of 30 male SD rats were randomly assigned to 3 groups.1. liver IP group. 2.heat preconditioning group. 3. IP+heatpreconditioning group. After intro venous administration of L-NAME, therat simulation model of othotopic liver transplantion was conducted. Thebile flow, serum ALT, AST, ALP level and the liver morphology was examined24 hours post- operation.Results: The administration of L-NAME impaired the bile flow, liverfunction and the morphology of liver in the group of liver IP, while thereis little impact on the group of heat preconditioning. The outcome ofthe combined preconditioning is worsen than the heat preconditioninggroup.Conclusion: L-NAME inhibited the production of NO, dramatically impactthe early protective effects of the ischemic preconditioning and thecombined protection with IP and heat preconditioning. While this showlittle influence on heat preconditioning.
|
PDF Full Text Request