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Nuclear factor-KB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft

World Journal of Gastroenterology 2005年第44期11卷 6960-6967页

作者： Ming-Qing Xu Xiu-Rong Shuai Mao-Lin Yan Ming-Man Zhang Lu-Nan Yan Department of General Surgery West China Hospital Sichuan University Chengdu 610041 Sichuan Province China Department of General Surgery Sichuan Provincial Hospital Chinese People's Armed Police ForcesLeshan 640014 Sichuan Province China

AIM： To evaluate the protective effect of NF-kB decoy oligodeoxynucleotides （ODNs） on ischemia/reperfusion （I/R） injury in rat liver graft. METHODS： Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-kB decoy ODNs or scrambled ODNs. NF-kB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation, respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-kB activity in the liver graft was analyzed by electrophoretic mobility shift assay （EMSA）. Hepatic mRNA expression of TNF-α, IFN-γ and intercellular adhesion molecule-1 （ICAM-1） were determined by semiquantitative RT-PCR. Serum levels of TNF-α and IFN-γ were measured by enzyme-linked immunosorbent assays （ELISA）. Serum level of alanine transaminase （ALT） was measured using a diagnostic kit. liver graft myeloperoxidase （MPO） content was assessed. RESULTS： NF-kB activation in liver graft was induced in a time-dependent manner, and NF-kB remained activated for 16 h after graft reperfusion. NF-kB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-kB decoy ODNs significantly suppressed NF-kB activation as well as mRNA expression of TNF-α, IFN-γ, and ICAM-1 in the liver graft. The hepatic NF-kB DNA binding activity [presented as integral optical density （IOD） value] in the NF-kB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat （2.16±0.78 vs 36.78 ±6.35 and 3.06±0.84 vs 47.62± 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P〈0.001）. The hepatic mRNA expression level of TNF-α, IFN-γ and ICAM-1 rpresented as percent of β-actin mRNA （%）] in the NF-kB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat （8.31 ±3.48 vs 46.37±10.65 and 7.46± 3.72

关键词： Hepatic ischemia/reperfusion injury NF-kB liver graft

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Effect of ulinastatin donor-pretreatment on liver graft during cold preservation in rats

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Chinese Medical Journal 2011年第4期124卷 574-580页

作者： MAO Jie ZHANG Lin SONG Ai-lin CHEN Xiao ZHANG You-cheng Department of General Surgery Lanzhou University Second Hospital Lanzhou Gansu 730030 China

Background Donor-pretreatment with ulinastatin may influence the liver graft during cold preservation. The aim of this research was to determine whether pretreatment of donor liver with Ulinastatin can attenuate cold preservation injury,and to explore the mechanism by which Ulinastatin affects the donor liver *** One hundred and forty-four Wistar rats were divided into the Ulinastatin treatment group （T group） pretreated with Ulinastatin 50 000 U/kg and control group （C group） treated with 0.9% normal saline via peritoneal injection prior to the anesthetization. After the abdominal cavity was opened and perfused with cold Ringer＇s lactate solution, the liver was harvested. The harvested liver was preserved in cold Ringer＇s lactate solution for 0, 2, 6, 24 hours, at which time the liver tissue was sampled for determination of dry weight and wet weight, Na＋-K＋-ATPase and Ca2＋-ATPase activity, lactic acid dehydrogenase （LDH） activity, lactic acid and malondialdehyde levels. Light microscopy and electron microscopy were used to observe liver morphology. The liver cold-preservation solution was taken for measurement of aspartate aminotransferase （AST） and alanine transaminase （ALT） levels. Correlation between ATPase activity and lactic acid level was analyzed by SPSS 13.0 for *** The morphology in the T group had improved cell boundaries vs. The C group at each time point. Dry weight to wet weight in the T group was lower than in the C group at 6 hours （P 〈0.05）, but the difference was not significant at 24 hours. ALT levels in the T group were lower than that in the C group at 6 hours （P 〈0.05） and 24 hours （P 〈0.01）. AST levels in the T group were lower than those in the C group at 2 hours （P〈0.05）, 6 hours （P 〈0.01） and 24 hours （P 〈0.01）.Na＋-K＋-ATPase activity in the T group was higher than in the C group and the mean difference between two groups was significant at 0 hour （P 〈0.05） and 2 hours （P 〈0.05）. Ca2＋-ATPase activity in the T group was

关键词： Ulinastatin donor pretreatment liver graft cold preservation injury

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Different ischemic preconditioning for rat liver graft: protection and mechanism

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Hepatobiliary & Pancreatic Diseases International 2003年第4期2卷 509-512页

作者： Shui-Jun Zhang Chang-Ju Zhu Yong-Fu Zhao Jie Li Wen-Zhi Guo the Department of Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China Department of Surgery First Affiliated Hospital Zhengzhou University Zhengzhou 450052 China. zhangshuijun@***

OBJECTIVE: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft. METHODS: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E_1), experimental group 2 (group E_2), and experimental group 3 (group E_3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E_1: 5-minute ischemia and 10-minute reperfusion; Group E_2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E_3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-α and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion. RESULTS: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-α in the experimental groups E_1, E_2, and E_3 were significantly lower than in the control group (Pliver graft injury by decreasing apoptosis of hepatocytes and production of TNF-α. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a bette

关键词： rat liver transplantation apoptosis tumor necrosis factor α reperfusion injury liver graft

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Using old liver grafts for liver transplantation: Where are the limits?

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World Journal of Gastroenterology 2014年第31期20卷 10691-10702页

作者： Carlos Jiménez-Romero Oscar Caso Maestro Félix Cambra Molero Iago Justo Alonso Cristina Alegre Torrado Alejandro Manrique Municio Jorge Calvo Pulido Carmelo Loinaz Segurola Enrique Moreno González Service of General and Digestive Surgery and Abdominal Organ Transplantation "Doce de Octubre" University Hospital

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

关键词： Old liver donors liver transplantation Aging liver liver graft liver disease Aging Donor management Septuagenarian donors Octogenarian donors

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Reuse of liver grafts following the brain death of the initial recipient

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World Journal of Hepatology 2014年第6期6卷 443-447页

作者： Hideaki Tanaka Vivian C McAlister Mark A Levstik Cameron N Ghent Paul J Marotta Douglas Quan William J Wall Multi-Organ Transplant Program London Health Sciences CentreLondonOntario N6A 5A5Canada Department of Pediatric Surgery Faculty of MedicineUniversity of TsukubaTsukuba CityIbaraki 305-8575Japan Canadian Armed Forces Health Service OttawaOntario K1A 0K2Canada

AIM: To determine if there is a reasonable prospect of success of a re-use liver ***: We systematically searched for reports of liver graft re-use using electronic searches of PubMed and Web of Knowledge. We performed hand searches of references lists of articles reporting re-use of ***: A systematic review of the literature reveals 28 liver transplantations using previously transplanted grafts. First and second recipients ranged in age from 4 to 72 years and 29 to 62 years respectively. liver disease in the first recipient was varied including 5(18%) patients with fulminant liver failure who died subsequently of cerebral edema. The second transplanta-tion was performed after a median interval of 5 d(one day-13 years). Viral hepatitis was present in 3(11%) of the initial recipients and in 8(29%) of final recipients. Hepatocellular carcinoma was present in 6(21%) of the final recipients. Early survival after the final transplantation was 93%, whereas long-term survival was 78% with a mean follow-up of 23.3(3-120) ***: Outcomes of transplantation using previously transplanted grafts in this select population are similar to those seen with conventional grafts.

关键词： Reuse liver graft Brain death liver transplantation

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Emergency re-routing of anterior sector venous outflow for right lobe living donor liver transplantation including the middle hepatic vein

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Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 325-327页

作者： Kenneth SH Chok See Ching Chan Chung Mau Lo Sheung Tat Fan Department of Surgery Queen Mary Hospital The University of Hong Kong State Key Laboratory for liver Research

BACKGROUND:Controversy remains over whether the middle hepatic vein should be included in the liver graft in right liver living donor liver *** in the anterior sector of a right liver graft can cause graft malfunction,which is especially devastating in the case of a graft with marginal size in relation to recipient body size on top of poor pre-transplant recipient *** case we report here highlighted the importance of the middle hepatic vein in right liver living donor liver ***:We illustrated the rectification of outflow obstruction of the middle hepatic vein in the anterior sector of right liver graft caused by technical error during *** rectification was performed with emergency re-routing using an artificial ***:Congestion in the anterior sector of the graft improved immediately and the patient’s postoperative liver function test results improved ***:The middle hepatic vein is important for effective drainage of the anterior sector of a right liver *** re-routing technique described in the report can also be applied to cases in which the middle hepatic vein is injured during hepatectomy requiring immediate reconstruction.

关键词： Gore-Tex graft vein graft liver graft cirrhosis hepatitis B infection

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Intestinal microbiota dysbiosis and liver metabolomic changes during brain death

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Journal of Intensive Medicine 2023年第4期3卷 345-351页

作者： Ruolin Tao Wenzhi Guo Tao Li Yong Wang Panliang Wang Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina Henan Key Laboratory for Digestive Organ Transplantation Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina Department of Biliary Surgery Nanyang Central HospitalNanyang 473009HenanChina Department of Anesthesiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina Department of Breast Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina

Background Whether a causative link exists between brain death(BD)and intestinal microbiota dysbiosis is unclear,and the distortion in liver metabolism associated with BD requires further *** A rat model of BD was constructed and sustained for 9 h(BD group,n=6).The sham group(n=6)underwent the same procedures,but the catheter was inserted into the epidural space without *** contents and portal vein plasma were collected for microbiota sequencing and microbial metabolite *** tissue was resected to investigate metabolic alterations,and the results were compared with those of a sham ***α-diversity indexes showed that BD did not alter bacterial *** dysbiosis occurred after 9 h of *** the family level,Peptostreptococcaceae and Bacteroidaceae were both decreased in the BD *** the genus level,Romboutsia,Bacteroides,Erysipelotrichaceae_UCG_004,Faecalibacterium,and Barnesiella were enriched in the sham group,whereas Ruminococcaceae_UCG_007,Lachnospiraceae_ND3007_group,and Papillibacter were enriched in the BD ***-chain fatty acids,bile acids,and 132 other microbial metabolites remained unchanged in both the intestinal contents and portal vein plasma of the BD *** caused alterations in 65 metabolites in the liver,of which,carbohydrates,amino acids,and organic acids accounted for 64.6%.Additionally,80.0%of the differential metabolites were decreased in the BD group *** metabolism was the most significant metabolic pathway in the BD *** BD resulted in microbiota dysbiosis in rats;however,this dysbiosis did not alter microbial *** in liver metabolic function during extended periods of BD may reflect a continuous worsening in energy deficiency.

关键词： Brain death liver graft Microbiota Metabonomic

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