Objective To study the interaction and mechanism of prostaglandin I2 (PGI2) receptor/thromboxane A2 (TxA2) receptor (IP/TP) and cyclooxygenase-2 (COX-2) in ischemia reperfusion injury after liver transplantation of rat. Methods Rats were randomly divided into three groups: control group （n=16), orthotropic liver transplantation group （n=32) and nimesulide intervention group （n=32). The samples were obtained at 3 h, 6 h, 12 h and 24 h after operation. The expressions of COX-2, IP and TP mRNA were detected by RT-PCR. Immunohistochemistry was used to detect the localization and expression of COX-2. Hematoxylin Eosin staining was used to classify the injury extent of liver. Serum ALT and AST levels were detected to evaluate the changes of liver enzyme. Results COX-2 protein expression detected by immunohistochemistry in orthotropic liver transplantation group mainly distributed in the district of liver sinusoidal endothelial cells, liver cells and macrophage cells, which was significantly higher than control group and nimesulide intervention group. Expressions of IP mRNA, TP mRNA and COX-2 mRNA in the orthotropic liver transplantation group were significantly increased than those in control group (P＜0.05), and the ratio of IP/TP increased (P＜0.05). Expressions of IP mRNA and TP mRNA in nimesulide intervention group were significantly lower than that in the orthotropic liver transplantation group at 6 h and 12 h after operation (P＜0.05), and the ratio of IP/TP decreased at 3 h, 6 h and 24 h after operation (P＜0.05). The expression of COX-2 mRNA in nimesulide intervention group was significantly lower than that in the orthotropic liver transplantation group at 6 h, 12 h and 24 h after operation. In orthotropic liver transplantation group liver injury was obvious by HE staining, and more severve than that in nimesulide intervention group. Serum AST (each time) and ALT (3 h, 6 h and 12 h) levels in the orthotropic liver transplantation group were significantly higher than that in control group and nimesulide intervention group (P＜0.05) and peaked at 6 h after operation. Conclusion The balance of IP/TP takes part in and plays an important role in the ischemia reperfusion injury of liver transplantation. Changing imbalance of IP/TP may reduce liver transplantation ischemia reperfusion injury by inhibiting COX-2 expression.
【Abstract】 Objective To study liver regeneration of the non-ligated liver lobes following portal branch ligation (PBL). Methods Sixty male Wistar rats were randomly divided into PBL group and sham operation (SO) group. Under ether anesthesia, the rats were subjected to PBL and sham operation, respectively. The animals were sacrificed on the 1st, 2nd, 3rd, 7th and 14th day respectively. The blood sample was collected from heart and the livers were harvested to determine serum alanine aminotransferase (ALT) levels and total liver weight, respectively. The hepatic histopathology was studied through light microscopy. The number of liver cell nuclear mitosis index was counted. The number of proliferative cell nuclear antigen (PCNA) index was counted by immunohistochemistry. The hepatic ultrastructural changes were studied under electron microscope. Results ①Elevated serum ALT level was observed in the first postoperative day in PBL group compared with SO group (P＜0.01)， but began to recover in the second day. ②No significant total liver weight change in PBL group and SO group were found. ③Liver cell nuclear mitosis index and PCNA index were markedly increased in PBL group compared with SO group in day 1-3 postoperative day (P＜0.01). It reached the peak in the second day and decreased slightly in the 3rd day, but still higher than SO group, then gradually return to normal lately. Conclusion The ligation of left portal branch can induce active regeneration of hepatic cell of non-ligated liver lobes in rats. The regeneration of non-ligated liver lobes may restore previous total liver weight. The ligation of 75% portal branch does not affect liver function and may be safely performed. The portal branch ligation in rats may be used as an animal model in study of liver regeneration.
【 Abstract 】 Objective To explore the effect of gamma-globulin in evaluating hepatic functional reservation in patients with liver tumor. Methods Serum protein electrophoresis (SPE) was performed on 30 patients with liver tumor to get gamma-globulin and preoperative Child-Pugh classification. Then the relations between gamma-globulin and preoperative and postoperative Child-Pugh classification were studied. While with gamma-globulin as evaluating standard, the validity compared with Child-Pugh classification were studied. Results The gamma-globulin was lower in classification A patients 〔（ 21.053 3 ± 6.001 4)% 〕 than that in classification B 〔 (28.800 0 ± 8.672 5)% 〕 before operation. While the gamma-globulin 〔 (21.022 0 ± 5.354 6)% 〕 of classification A patients after operation was also lower than that of classification B/C 〔 (29.556 0 ± 7.698 5)% 〕 . These differences were significant (P ＜ 0.05). With gamma-globulin gt;30% as evaluating standard ， the sensitivity and specificity were 80.00% and 96.00%, respectively. Conclusion Gamma-globulin can reflect hepatic functional reservation in patients with liver tumor. Combining gamma-globulin and Child-Pugh classification can evaluate hepatic functional reservation more objectively.
ObjectiveTo investigate the relationship between hormone and liver regeneration.MethodsThe related literatures in recent years were collected and reviewed.ResultsHormone was related to liver regeneration significantly and participated the process of liver regeneration. It had a promotive or inhibitive role in liver regeneration.ConclusionHormone is one of the important factors in the regulation of liver regeneration.
Objective To investigate the effect of B7-1 and IL-12 gene expression on the immunogenicity of hepatocellular carcinoma (HCC) HepG2 cells. Methods Plasmids encoding B7-1 and IL-12 molecules were retrovirally introduced into human HCC cells,empty vector as control. PBLs were cocultured with HepG2/B7-1,HepG2/IL-12 and HepG2/neo cells. Three days later,PBLs were submitted to specific cytotoxicity test and nonspecific cytotoxicity test against K562 cells by MTT assay.Results HLA-Ⅰ molecules on PBLs were detected by FACS.HLA-Ⅰ molecules expressing on PBL cocultured with HepG2/B7-1,HepG2/IL-12 cells were enhanced by 16.95% and 14.71% than those of HepG2/neo group, respectively(Ｐ＜0.05). Specific cytotoxicity against HepG2/B7-1 cells was 12.5% higher than that of against HepG2/neo cell,while no increase in that of against HepG2/IL-12 cells. Cytotoxicities against K562 cells in HepG2/B7-1,HepG2/IL-12 groups were 19.38% and 14.78% higher than those of HepG2/neo group, but no significant difference between the first two groups.Conclusion B7-1 and IL-12 gene transfer could remarkably promote immunogenicity of hepatocellular carcinoma cells and induce b specific and nonspecific immunity against hepatocellular carcinoma in vitro.
Objective To research anesthetic management, pathophysiologic variation of adult-to-adult living donor liver transplantation (A-ALDLT) and to probe how to improve anesthetic quality of A-ALDLT. Methods The clinical data of 47 donors from Sep. 2005 to Jan. 2007 in West China Hospital were reviewed. Intraoperative vital signs, anesthetic management, perioperative serum levels of HGB， Alb， ALT， AST, TBIL， APTT， PT were measured， and complications were assessed. Results The physical condition of all donors were good before operations and were all in grade Ⅰaccording to ASA. Under general anesthesia of intravenous and inhalation, electrocardiogram, O2 saturation, blood pressure and body temperature were continuously monitored. A radial arterial catheter and a central venous catheter were placed. Blood lavement was utilized intraoperatively in all patients. All donors maintained stable life signs intraoperatively. The average intraoperative blood losses was （603.13±317.00） ml, and donors were transfused with autologous blood 〔(381.25±171.15) ml〕, with only 4 donors required homologous blood transfusion. HR and mean arterial blood pressure (MAP) showed no significantly variations intraoperatively (Pgt;0.05). Compared with controlled central venous pressure (CVP) before and right after hepatectomy, CVP increased significantly (P＜0.05) when intubation and abdomen-closing were carried. After hepatectomy and on the first day after operation, HGB and Alb decreased significantly (P＜0.05); ALT, AST and TBIL increased significantly (P＜0.05). Right after hepatectomy, PT increased instantly and significantly (P＜0.05); On the first day after operation, APTT began to increase significantly (P＜0.05). All donors came around completely and were extubated in the liver transplantation intensive care unit on the first day after operation. There were 3 cases (6.38%) of postoperative complication, which were biliary leakage, portal vein thrombosis and serious pleural effusion. Those 3 donors were cured after treatment. Conclusion Inhalation and intravenous general anesthesia of propofol, remifen-tanil and isoflurane can maintain stable life signs and reduce liver injury. Steady anesthesia, sufficient oxygenation and effective blood protection measures, for example, by decreasing CVP to prevent bleeding and by reclaiming autologous blood to avoid transfusing homologous blood, are keys for the safety of the donor and the prevention of complications.
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.
Objective To explore the liver regeneration following partial liver transplantation. MethodsPartial liver transplantation in the rats were established, three experimental groups were: Ⅰ=control, partial liver resection; Ⅱ=orthotopic liver transplantation (OLT); Ⅲ=partial orthotopic liver transplantation (POLT). Liver function test, morphological investigations and liver regeneration were performed in different time after transplantation. The regenerative response of transplanted partial liver graft in rats were evaluated by Flow Cytometry and compared it to liver regeneration following resection.Results The serum concentrations of ALT, BILI increased in one week, but returned gradually to normal level within one month after transplantation. Large numbers of mononuclear cells infiltrating into the portal areas. Hepatocyte necrosis was observed on day 14 after transplantation. On day 30, the parenchyma cell showed a nearly normal appearance, bile duct proliferation was seen in portal areas. In addition, after liver resection and POLT some diploid hepatocytes were found. Dilation of the central veins, adjoining sinusoids and interlobar veins were seen in group Ⅲ. The partial liver graft is capable of regeneration similar to the situation following partial hepatectomy. The peak of liver regeneration was seen on day 1,2,4 following a hepatectomy and POLT and OLT, respectively.Conclusion The transplanted liver shows the same and/or enhanced regeneration compared to controls. There are several possible explanations for the slight delay in achieving the maximal regenerative response in rats undergoing the POLT and OLT. These may include damage that is induced by the operation itself, preservation, and reperfusion injuries. These suggest that this be caused by activation of the immune system and it might be related to the regulation of cytokines and hormone.
Objective To evaluate the suitability of the biodegradable microsphere encapsulation of adenovirus as a targeting vector for gene therapy of hepatocellular carcinoma. Methods Encapsulate the recombinant adenovirus in PLG 〔poly (lactic/glycolic)〕 copolymer by the solution evaporation method, the release test and the bioactivity of viruses incorporated in vitro were studied. Results More than 19.3% of adenovirus was encapsulated in PLG microspheres. The release test shows that the adenovirus was released for more than 200 h, 50% were shed within the first 100 h, and their activity was retained. Conclusion Recombinant adenovirus can be formulated in a polymer preparation of PLG with retention of bioactivity. It may be a valuable vector for the gene therapy of liver cancer.
Objective To Investigate the indications, surgical technique and perioperative management of orthotopic liver transplantation.Methods Orthotopic liver transplantation was successfully performed on a unresectable liver cancer on caudate lobe, 2 cases with Caroli’s disease and 7 cases with advanced liver cirrohosis. A 11 year’s old girl with Caroli’s disease was performed on one reduced size liver transplantation (RSLT). Results The recovery of liver graft function was good after the operation in those patients without perioperative death. The case of liver cancer died of recurrent cancer on the 139th postoperative day, 1 case died of severe fungus infection and one died of gastric stress ulcer perforation, other 7 cases recovered well without complications. Conclusion The results suggest that unresectable central liver cancer, terminal liver cirrohosis or benign liver diseases combined with severe liver disfunction are good indications for liver transplantation. Good surgical technique and perioperative management are key points to succucess of the liver transplantation.