Dissertation > Excellent graduate degree dissertation topics show

The Protective Effect of Hepatocyte Growth Factor and Carbamide Peroxide Preconditioning on Liver Ultrastrure Injury Followed Ischemia Reperfusion in Rats

Author: WangXiaoKe
Tutor: HanXiChun
School: Jilin University
Course: Clinical
Keywords: Liver Reperfusion injury Ultrastructure Rats
CLC: R657.3
Type: Master's thesis
Year: 2006
Downloads: 55
Quote: 0
Read: Download Dissertation

Abstract

Objective:In Pringle’s maneuver during liver surgeryand liver transplantation, ischemia-reperfusion (I/R) isan unavoidable process, and protection against hepaticI/R injury is a major unresolved problem. Therefore,various pharmacologic approaches to prevent hepatic I/Rinjury are currently under trial.Its mechanisms remain poorly understood.The previousstudy concentrated on liver energy metabolism anddestroyed structure,including cytomicrosome damaging,Na+-K+ pump activity depressing,endoproteinase inhib-iting,phospholipase inhibiting,Kupffer cell activating,oxygen free radical suddenly increasing, endothelialcell damaging,neutrophil activating.Hepatocyte growth factor (HGF) was purified as apotent mitogen for rat hepatocytes in primary culture andis believed to be the most physiological hepatotrophicfactor that triggers liver regeneration. HGF is one ofthe largest disulfide-linked cytokines, consisting of a60-kDa heavy chain and a 35-kDa light chain. Human HGFis synthesized as a single polypeptide chain precursorof 728 amino acid residues that has an appreciablehomology with plasminogen, and it is processed proteol-ytically to release an N-terminal signal peptide of 31amino acids and to generate an active heterodimer aftersecretion. The novel serine protease HGF activator areresponsible for the latter extracellular processing. HGFstimulates the proliferation of rat hepatocytes inprimary culture .It also stimulates the growth of variousepithelial cells, endothelial cells, and some kinds ofmesenchymal cells. HGF inhibits the proliferation ofseveral tumor cell lines and induces apoptosis of someof them. It also has motogenic, morphogenic, anti-apoptotic, angiogenic, and immunoregulatory activities.The receptor of HGF is the product of c-met proto-oncogenewith tyrosine kinase activity that mediates the trans-duction of multiple biological signals of HGF. Duringliver regeneration, HGF gene expression in the liver,spleen, and lung and HGF levels in the blood and liverincrease prior to the induction of liver DNA synthesis.)H2O2 is a oxygen free radical released by thecarbamide peroxide,but it can reduce liver cell to gener-ate endogenous protector protein before every damagment.and it can provide efficient oxygen level to pretect theliver in Pringle’s maneuver during liver surgery andliver transplantationWe want to show each damaged liver degree by electronmicroscope and liver functional examination , looking forthe most reasionable administration pathway.Methods:50 rats were randomly divided into fivegroups: Hepatocyte growth factor preconditioning groups(n=10),Carbamide peroxide preconditioning groups (n=10),Both of drugs preconditioning groups(n=10), ischemia-reperfusion groups(n=10), nonischemic controls group(n=10). All groups were given drugs corresponding tothemselves in the last 30 minutes,and hepatic IR injuryrats were induced by 60 minutes of partial liver ischaemia.Finally open the vascular clip to recycle the blood.ultrastructual changes of liver were studied by electronmicroscope.Results: A 组 : there are many chondrosomes in thekytoplasm. their structures are integrity. cell organsare integrity. endocytoplasmic reticulum and chondrosomecan be seen.they were normal. The nuclear membrane andplasm-osomecan be seen clearly. B 组:cell body is notintegrity and endochylema is rarefaction and autolysis.endothelial cell have been highly swell and apoptosis.Itcan be seen membranolysis and a lot of red cells. The cellnuclear has the cavitation and pyknosis change. Thechondrosomes are highly swell and cavitation.TheCristaes of the chondrosomes are not integrity.The roughendoplasmic reticulums are broken to pieces. Theendocytoplasmic reticulum’s base material iscavitation.C group: cell body and endothelial cell havea little swell. endocytoplasmic reticulum andchondrosome can be seen. The cell nuclear is normal.D group: cell body and endothelial cell have a littleswell. The endocytoplasmic reticulum and chon-drosomecan be seen. The cell nuclear is normal. In the cellintracytoplasm,we can see many cytotoxicity objects.rough endoplasmic reticulums are broaden.E group:cellbody and endothelial cell is normal. cell organs areintegrity. endocytoplasmic reticulum and chondrosome canbe seen.they were normal.The calculating analytic result of microscopepicture: Compared with the normal control group and otherfour groups ,there were significant difference ( P<0.05).Removing the normal control group,the quantity ofspecific surface area in the I-R group is the largest thanthat of other three groups.It is also significantdifference. the quantity of specific surface area in theE groups is super lowest than that of the C and D groups.itis very different(P<0.05).But there is no significantdiference between C and D groups(P>0.05).The definition of the specific surface area: It iseasy to say that the specific surface area is the quantityof surface area /the quantity of unit volume.When it isequal to 1,the figure is a subsphaeroidal. If thechondrosome has a normal shape ,the quantity of thespecific surface is between 0.8and 0.9.The quantity of the ALT and AST in the blood serum:Compared with the normal control group and other fourgroups ,there were significant difference ( P<0.05).Removing the normal control group,the quantity of the ALTand AST in the blood serum in the I-R group is the largestthan that of other three groups.It is also significantdifference. the quantity of the ALT and AST in the bloodserum in the E groups is super lowest than that of theC and D groups.it is very different(P<0.05).But there isno significant diference between C and D groups(P>0.05).Conclusions:With the progress of some researches,pre-treatment of drugs have many advandages which aresafety, efficient and potential.We can use Hepatocytegrowth factor and carbamide peroxide to preconditiononliver. ultrastructual changes of liver were studied byelectron microscope.And we can conclude that Defferentmechanisms have two drugs that can take effect intosynergism.According to this hypothesis,these liverprotective additives can be proved to have playedsignificant role in many kinds of animal experiments inthe future.

Related Dissertations

CLC: > Medicine, health > Surgery > Of surgery > Abdominal surgery > Liver and liver tube
© 2012 www.DissertationTopic.Net Mobile