【Abstract】ObjectiveTo investigate the protective effects and the impact on the expression of Bcl-2 and Caspase-3 mRNA by Panax notoginseng saponins (PNS) preconditioning in rat liver transplantation. MethodsMale Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT) and were divided into PNS preconditioning group (PNS group) and NS control group (NS group) randomly according to whether PNS was injected by venous (50 mg/kg) 1 h before liver grafts harvesting. The animals were respectively killed 2 h, 6 h and 24 h after reperfusion. Plasma samples were collected for ALT and AST test. Liver tissues were collected to detect histological changes, apoptosis and the expression of Bcl-2, Caspase-3 mRNA. ResultsThe serum levels of ALT and AST and the apoptosis index (AI) of liver tissue in PNS group were lower than those in NS group’s significantly (P<0.05) at 2 h, 6 h and 24 h after reperfusion. The expression of Bcl-2 mRNA was enhanced significantly in PNS group at 6 h, 24 h after reperfusion and the expression of Caspase-3 mRNA was decreased significantly in PNS group at 2 h, 6 h after reperfusion as compared with NS group’s(P<0.05). ConclusionPNS preconditioning can attenuate liver grafts ischemia/reperfusion injury and apoptosis of hepatocytes. Affecting expression of Bcl-2 and Caspase-3 genes may be one of the mechanisms of PNS antiapoptotic effects.
【Abstract】 Objective To investigate the expression patterns of vascular endothelial growth factor (VEGF) mRNA as markers for isolated tumor cells in the peripheral blood of patients with hepatocellular carcinoma (HCC) following liver transplantation, and to evaluate the correlation between VEGF and the recurrence and metastasis of HCC following liver transplantation. Methods In this prospective study, 97 patients were divided into four groups according to the pathological results: HCC following liver transplantation group (HCC+LT group, n=53), advanced HCC group (n=8), benign liver diseases group (n=26) and healthy volunteers group (n=10), among which the 53 cases in HCC group were collected from April, 2002 to December, 2003. RNA was purified from the peripheral blood of the other 44 control patients and also from the patients in HCC group before, during and after liver transplantation in order to study the expression specificity of VEGF mRNA in HCC patients and its dynamic change during perioperative period. The correlation between VEGF and the tumor recurrence and metastasis was also analyzed by fluorescent quantitative reverse transcriptase and polymerase chain reaction (FQ RT-PCR). Results VEGF mRNA could be used as marker of isolated tumor cells for its high specificity. The positive rate of VEGF mRNA in HCC group and in advanced HCC group were 37.5% and 75.0%, respectively, which were significantly higher than that in benign liver diseases group (11.5%) and healthy volunteers group (10.0%), P<0.01. The presence of preoperative VEGF mRNA and the consistent presence of postoperative VEGF mRNA might be relevant with the recurrence and metastasis HCC following liver transplantation (P<0.01). Conclusion The presence of preoperative VEGF mRNA and the consistent presence of postoperative VEGF mRNA may predict the recurrence and metastasis HCC following liver transplantation.
【Abstract】ObjectiveTo compare the hemodynamic changes during operation of portal venous intubation or splenic venous intubation in extracorporeal venous bypass of swine orthotopic liver transplantation.MethodsThirty couples of healthy Duloke pigs were selected to perform orthotopic liver transplantation. According to the difference of cannula vessel of portal venous system during extracorporeal venous bypass, these pigs were divided into two groups: portal venous intubation group (n=15) and splenic venous intubation group (n=15). Hemodynamic changes were monitored continuously.ResultsTwo recipients died in portal venous intubation group, one died of unsmooth bypass in the operation, the other died of DIC. In splenic venous intubation group there was only one recipient death, who died of hemorrhagic shock. The time of anhepatic phase of splenic venous intubation group was (44.5±7.6) min, it was significantly shorter than portal venous intubation group(51.5±8.7) min(P<0.05). Hemodynamic changes in phase Ⅲ and phase Ⅳ of portal venous intubation group were significantly different with that of splenic venous intubation group(P<0.05). ConclusionApplication of bypass through splenic venous intubation during extracorporeal venous bypass of swine orthotopic liver transplantation can shorten the time of anhepatic phase, keep the hemodymamics relative stable in operation, and reduce the occurrence of postoperative correlative complication. It is an effective venovenous bypass pathway.
ObjectiveTo provide the reliable model in the rat for the study of liver transplantation.MethodsA surgical experience with one hundred and fifty orthotopic liver transplants in rats was reviewed,meanwhile a simple method with biliary extradrainage as well as bile collection was introduced.Results The operative successful rate was 93.8%(91/97),the survival rate after one week was 85.9%(55/64),the recipient underwent an anhepatic period of 19 min,the operative time of donor and recipient were 37 min and 56 min,respectively.ConclusionThe result indicates that the model is reliable in the study of liver transplantation.The hard work and meticulous surgical performance are the key to successful operation.
Objective To validate the mechanism of effect of hepatic artery ischemia on biliary fibrosis after liver transplantation and the prevention method. Methods Eighteen male dogs were established into the concise auto orthotopic liver transplantation models and assigned into three groups randomly: hepatic artery ischemia (HAI) group, TBB group (transferred the blood by a bridge duct ) and control group, each group contained 6 dogs. After opening portal vein, the samples were cut from liver in each group at the time of 6 h, 3 d and 14 d. The pathological modifications of intrahepatic bile ducts were observed and expression of transforming growth factor-β1 (TGF-β1) were detected in the three times. Expressions of Smad3 and phosphate-Smad3 as well as mRNA of α-smooth muscle actin (α-SMA) in intrahepatic bile ducts were detected 14 d after opening portal vein.Results Compared with control group, the collagen deposition and lumens stenosis in biliary vessel wall were more obviously in HAI group. In TBB group, the pathological modifications were slighter compared with HAI group. The positive cell index of TGF-β1 reached peak on day 3 after opening portal vein, then decreased in TBB group, and which in HAI group kept increase and was significantly higher than that in TBB group (Plt;0.05). The expression level of phosphate-Smad3 and transcriptional level of α-SMA mRNA were 1.04±0.13 and 1.12±0.55 in TBB group on day 14 after opening portal vein, which were significantly higher than those in control group (0.59±0.09 and 0.46±0.18) and lower than those in HAI group (1.82±0.18 and 1.86±0.73), the diversities among three groups were significant (Plt;0.05). There was not significant difference of expression of Smads among three groups (Pgt;0.05). Conclusions Hepatic artery ischemia could increase the deposition of collagen fibers and the transdifferentiation of myofibroblast in bile duct and result in the biliary fibrosis by activating the TGF-β1/Smads signaling pathway. The bridging bypass device could lessen the biliary fibrosis caused by hepatic artery ischemia by inhibiting the activation of TGF-β1/Smads signal transduction passageway.
Objective
To investigate the risk factors of early allograft dysfunction (EAD) following C-Ⅱ donation after cardiac death (DCD) liver transplantation.
Methods
The data of 46 donors and recipients of C-ⅡDCD liver transplantation between March 2012 and August 2015 were retrospectively analyzed. The baseline data such as democracy, death cause, donor warm ischemic time (DWIT) and cold ischemic time (CIT) in EAD group and the non-EAD group (control group) was compared, and whether these factors were risk factors of EAD was investigated by univariate and multivariate analyses. Statistical cut-off values for significant factors of the unfavorable analysis were defined by receiver operating characteristics (ROC) analysis. The 6-month and 1-year graft survival rate were compared.
Results
The EAD group had a longer DWIT compared with the group [(17.6±4.7) and (12.7±6.2) minutes, P=0.009]; meanwhile, the EAD group had a longer CIT compared with the control group [(13.7±4.7) and (11.0±3.5) hours, P=0.020]. The other factors in both groups showed no statistical significance (P>0.05). The ROC curve revealed the cut-off values of DWIT and CIT were 17.50 minutes [area under the curve (AUC)=0.713, P=0.020] and 9.85 hours (AUC=0.723, P=0.015), respectively. The multivariate logistic regression analysis showed the DWIT [odds ratios (OR)=1.340, 95% confidence interval (CI)(1.042, 1.654), P=0.008] and CIT [OR=1.396, 95% CI (1.075, 1.698), P=0.015] were all independent risk factors of EAD. The 6-month and 1-year graft survival rate of the EAD group and the control group was 85.7% vs. 92.3% (P=0.607) and 71.4% vs. 84.6% (P=0.587), respectively.
Conclusions
EAD may occured in C-Ⅱ donors with DWIT≥17.50 minutes or CIT≥9.85 hours in DCD liver transplantation. The livers can be used as a resource for clinical use and also have a good outcome.
Objective To summarize the application and advancement of liver transplantation for hepatic metastasis from neuroendocrine tumor. Methods Domestic and overseas publications on the study of liver transplantation for hepatic metastasis from neuroendocrine tumor in recent years were collected and reviewed. Results Liver transplantation can offer good relief of symptoms, long disease-free intervals, and potential cure in individual patients with hepatic metastatic tumor. Important selection criteria are well-differentiated tumors and a low proliferation rate (Ki67<10%). Conclusion In carefully selected patients with metastatic neuroendocrine tumors, liver transplantation is an appropriate option.
【Abstract】Objective To introduce the birth and development of model of endstage liver disease (MELD) and evaluate its effect on liver transplantation(LT) as a new scoring system. Methods Literatures of MELD applied in LT were analyzed retrospectively. Results MELD scoring system was used for predicting the prognosis of patients with endstage liver disease and the death risk of candidates on waiting LT extensively and the order of organ sharing was determined by its predicable results. Conclusion MELD has been had a successful initial implementation for predicting the shortterm survival probability and mortality in patients with endstage liver disease, and meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, which has been proven to be a powerful tool for auditing the liver allocation system.
Objective To establish the rat orthotopic liver transplantation model by characterizing the blood supply of hepatic artery with the Cuff skill and the modified arterial sleeve anastomosis, to explore the possible mechanisms of acute rejection and the express of Fractalkine (Fkn) in the early stage after hepatic allograft operation. Methods SD rats were selected as donors and Wistar rats as receptor for the rejection model of orthotopic liver transplantation. Recipient rats were divided into 2 groups randomly after operationand the drugs were given intraperitoneally once a day in each group. In the experimental group, cyclosporine A (CsA) was delivered with 3 mg/kg. In the control group, only normal saline was given with 3 ml/kg. Condition of survivals were observed. The rejection actvity index (RAI) and the expression of Fkn of liver tissue were observed after 3rd, 5th and 7th days in 5 rats. The rest of rats in each group were fed and given drug or normal saline until they were died and the mean survival time were recorded. Results There were 18 survivals in control group, and 19 in experimental group after liver transplantation. Condition of survivals in experimental group was better than that of control group. The mean survival times of experimental group(19.50±4.51 days) was significantly longer than that of control group(7.60±1.60 days), showing statistically significant difference (P<0.05). After 3rd, 5th and 7th days of transplantation, RAI of control group were 3.80±0.35,5.90±0.87 and 7.50±1.30,respectively;RAI of experimental group were 3.10±0.21,3.90±0.41 and 4.50±0.52.Therewasstatistically significant difference in RAI between 2 groups on the 7th day after transplantation (Plt;0.01). On the 3rd,5th and 7th days after transplantation, the Fkn of control group was 8.20±0.57,21.30±3.30 and 25.70±4.91, and that of experimental group was 8.30±0.56,10.30±0.67 and 11.70±1.23. There were statistically significant differences in Fkn between 2 groups on the 5th, 7th days after transplantation (Plt;0.01). Conclusion Fkn is a participant inacute rejection after the rat orthotopic liver transplantation and can be chosen as a useful target in the diagnosis of acute rejection. CsA has immunosuppressive property in the condition of acute rejection in the rat orthotopic liver transplantation, which may be result from the decreased the level of Fkn.
Objective To observe the effects of Thymosin α1 (Tα1) on acute rejection after liver transplantation and immune function of T cells. Methods Twenty recipients of liver transplantation due to primary hepatic carcinoma were divided into two groups: Tα1 group (n=10) and control group (n=10). Tα1 group received subcutaneous injection of Tα1 1.6 mg on the first day after liver transplantation and then twice a week for at least one month. Both Tα1 group and control group took same immunodepressants. Core biopsies were carried to compare the incidence rate of acute rejection between Tα1 group and control group. Peripheral T cellular immune function in these two groups was detected on 1 d before, 1 week, 2 weeks and 1 month after transplantation. Results There was not significant difference of incidence rate of acute rejection between Tα1 group and control group (Pgt;0.05). In the Tα1 group, CD4+, CD8+ lymphocyte cell counts and the CD4+/CD8+ ratio were significantly higher than those in the control group in 2 weeks and 1 month after transplantation (P<0.05). Conclusion Use of Tα1 in recipients who also takes rountine immunosuppressants dose not increase the risk of occurring acute rejection after liver transplantation. Tα1 can significantly increase CD4+, CD8+ counts and CD4+/CD8+ ratio, which shows that Tα1 may improve recipients’ cellular immune function.