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An Experimental Study Of Glycine Pretreatment On The Transplanted Rat Liver From Brain-Dead Donor

Posted on:2004-09-21Degree:MasterType:Thesis
Country:ChinaCandidate:J H ShiFull Text:PDF
GTID:2144360095950072Subject:General Surgery
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BackgroundLiver transplantation (LTx) has become the most effective treatment for the end-stage liver diseases.However, the shortage of donor organs restricts the development of clinic liver transplantation.Brain-dead donor(BDD) is the suitable organ origin to solve the problem. Brain death is the loss of all cerebral functions, which means death. Some data show that there are damages to the livers in a state of brain death both in function and morphology, which would become more serious after liver ischemic-reperfusion injury. So the experimental studies, which focus on the mechanism of the injury of the transplanted livers from BDD and its protection, are important to use BDD during LTx in an effective way. Now the mechanism of the injury of livers from BDD is not very clear and research on its protection is scarce.AimIn this study, the rat models using the brain death of donors and orthotopic liver transplantation (OLT) are established. Then the mechanism of the injury to livers from BDD and its protection are well discussed to investigate the theoretical basis of using BDD during LTx in an effective way.MethodsA total of 56 male Wistar rats were allocated into 4 groups of liver transplantation at random:living donors group(L),brain-dead donor group(B),glycine pretreatment group (G), strychnine and glycine pretreatment group(S).Group L were made in the standard model of orthortopic liver transplantation.For groups B,G and S,the brain death model was established in the donor and then liver transplantations were performed using microsurgical techniques as group L.Brain death was induced by inflating the balloon of a Fogarty 3F cather placed through a hole made in the skull and the rat state of brain death was confirmed by irreversible coma,abserice of respiratory and brain stem reflex' s,and flat line of EEG tracings.After establishment of brain death state, the lactate ringer solution(2ml) was injected into infrahepatic vena cava(IHVC) of the donors,with glycine(300mmol/l) dissolved in group GDuring liver cold rinse of donors and liver reperfusion of the recipients,the livers were treated by the lactate ringer solution,with glycine (5mmol/l) dissolved in group G or glycine (5mmol/l) and strychnine (5μ mol/1) dissolved in group S respectively.During the experiments,cold ischemic time,non-hepatic time and surgical operation time for both donors and recipients were recorded for all groups,the mean arterial pressure(MAP) and heart rate(R) for groups B,G and S were dectected to confirm the state of brain death at the same time.Before the cold rinse and at 2h and 6h after the reperfusion of portal vein(PV),blood samples were taken from IHVC to determine the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),tumor necrosis factor alpha(TNF-a) and hyaluronic acid (HA).At 6h after PV reperfusion,graft samples were fixed for electronstropy observation and the apoptosis of hepatocytes was detected by using TUNEL method.The results were expressed as mean±SD and the difference were considered significant at P<0.05. Statistical analysis was performed by using SPSS 10.0 software.Results1. Cold ischemic time, non-hepatic time, surgical operation time for donors and recipients among 4 groups did not vary significantly,P>0.05.2. Before or during the inflation of Fogarty balloon or confirmation of brain death, mean artery pressure (MAP) and heart rate (HR) did not differ for the donors of group B, G andS,P>0.05.3. At the time points before liver cold rinse or at 2h and 6h after PV reperfusion ,serum levels of ALT,AST,TNF-a and HA in group B were significantly higher than those in group L,P<0.05. While these parameters in group G showed significantly lower than those in group B or S,P<0.05.4. At 6h after liver reperfusion, serum levels of ALT,AST and HA were significantly higher in contrast to those at 2h after reperfusion for all groups,P<0.05,whereas serum level of TNF-a peaked at 2h and slightly decreased at 6h after reperfusion,P<0.05.5. Electron micro...
Keywords/Search Tags:rats, liver transplantation, brain death, glycine, Kiipffer cells, apoptosis
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