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γ-hydroxybutyrate protects the liver from warm ischemia-reperfusion injury in rat

Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 245-249页

作者： Zheng- Zhuan Wei and Sui-Sheng Xia wuhan, china institute of organ transplantation, tongji Hospital, tongji medical college, huazhong university of science and technology, wuhan 430030, china institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. weizhz@***

BACKGROUND: Ischemia-reperfusion (I/R) syndrome remains an important clinical consideration in hepatic sur- gery, hemorrhagic shock, and liver transplantation, -y-hy- droxybutyrate (GHB) has been reported to exert protective effects against ischemia-reperfusion injury to various or- gans. To investigate whether GHB protects the liver from warm ischemia-reperfusion injury, we performed this study in rats. METHODS: Thirty male Wistar rats were randomly divided into a sham-operation group, a control group, and three I/R groups pretreated with GHB, GHB plus naloxone or naloxone. After 30 minutes of partial ischemia, followed by 60 minutes of reperfusion in the liver, histomorphological and enzymological changes, lipid peroxidation, apoptosis, and the plasma level of endothelin-1 were observed. RESULTS: I/R increased the serum levels of alanine ami- notransferase, aspartate aminotransferase and lactate dehy- drogenase and the plasma level of endothelin-1 significantly (P<0.01), in addition to increase of apoptotic index (AI) from 0.28%±0.25% to 17.68%±1.91%. The levels of he- patic malondialdehyde were markedly increased, whereas the activities of superoxide dismutase were markedly de- creased. GHB pretreatment prevented the liver from warm ischemia-reperfusion injury significantly, but naloxone par- tially blocked this effect. CONCLUSION: GHB may significantly protect the liver from hepatic warm ischemia-reperfusion injury via several different mechanisms.

关键词： γ-hydroxybutyrate liver ischemia-reperfusion injury apoptosis

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Immune protection of auxiliary liver to other allograft: report of 3 cases

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Hepatobiliary & Pancreatic Diseases International 2003年第3期2卷 351-353页

作者： Nian-Qiao Gong Qi-Fa Ye the institute of organ transplantation, tongji Hospital, tongji medical college, huazhong university of science and technology, wuhan 430030, china institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. nqgong@***

OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patients undergoing auxiliary liver transplantation were analysed. RESULTS: The lower the concentration of immunosuppressive agent, the less the rejection and the milder the intensity in the 3 patients. The function of allograft after auxiliary liver transplantation was excellent. CONCLUSIONS: Patients are in a low immune reaction state after auxiliary liver transplantation. Auxiliary liver can protect other allografts by related immunological mechanisms. The side-effects of low-concentration immunosuppressive agents on auxiliary liver and other allografts are mild.

关键词： auxiliary liver transplantation immune protection allograft

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Apoptosis and proliferation of intrahepatic bil educt after ischemia-reperfusion injury

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Hepatobiliary & Pancreatic Diseases International 2004年第3期3卷 428-432页

作者： Wen-Hui Xu, Qi-Fa Ye and Sui-Sheng Xia institute of organ transplantation, tongji Hospital,tongji medical college, huazhong university of science and technology,wuhan 430030, china institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. jzxwh@***

BACKGROUND: In orthotopic liver transplantation, ische-mic-reperfusion is one of the most important factors thatcause the incidence of biliary complicance. The aim of thisstudy was to investigate the effects of ischemia reperfusionon epithelial cells apoptosis and proliferation of intrahepaticbile duct (IBD) (>20 μm).METHODS: 30-minute warm ischemia was applied to ratlivers respectively, and experiment was performed on days2,7, 14, 28 after reperfusion. Apoptosis was determined insitu by morphology and TUNEL, and cholangiocyte proli-feration was evaluated in situ by morphometry of liver sec-tions stained for cytokeratin-19 ( CK-19) and by prolifera-ting cellular nuclear antigen staining in liver ***: Two days after ischemia reperfusion, apoptosisof cells was observed in large intrahepatic bile ducts (>20μm) (5.6%±1.2%) , but the number of large intrahepaticbile ducts reduced (0.32 ±0.06). Seven days after ischemiareperfusion, the apoptosis index of cholangiocytes de-creased to 1.2%±0.3%, and the number of intrahepatic bileducts began to proliferate and returned to nearly normal onday ***: Ischemia reperfusion causes a decrease inthe number of intrahepatic bile ducts (>20 μm) as a resultof a higher rate of apoptosis and absence of initial prolifera-tion.

关键词： apoptosis proliferation intrahepatic bile duct epithelial cells

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Simultaneous pancreas-kidney transplantation with modified enteric drainage of exocrine pancreatic secretion

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Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 183-187页

作者： Bin Liu, Chang-Sheng Ming, Fan-Jun Zeng, Bo Sha, Zhi-Shui Chen, Zhong-Hua Chen and Shi Chen wuhan, china institute of organ transplantation, tongji Hospital, tongji medical college, huazhong university of science and technology, wuhan 430030 , china institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. binliu@***

BACKGROUND: As a valid therapeutic option for patients with type 1 diabetes mellitus (IDDM) and secondary dia- betic nephropathy, simultaneous pancreas-kidney trans- plantation (SPK) remains more undeveloped than other solid organ transplantations due to the restrictions of surgi- cal techniques especially the modes of exocrine pancreatic secretion. The aim of this paper was to summarize our sin- gle-center experience in SPK with modified enteric drai- nage (ED). METHODS: From June 2000 to July 2003, 10 patients with IDDM associated with uremia received SPK. The pancrea- tic allograft exocrine secretion was drained into the proxi- mal jejunum via a side-to-side duodenojejunostomy with- out Roux-en-Y anastomosis. Quadruple immunosuppres- sive regimen consisted of induction of tacrolimus (TAC) / cyclosporine (CsA), mycophenolate mofetil (MMF), ste- roids and antibodies, which included antilymphocyte glo- bulin (ALG) or anti-CD25 monoclonal antibody. RESULTS: ED-SPK without Roux-en-Y anastomosis was successful in all 10 patients without serious complications such as pancreatitis, graft thrombosis and pancreatic fistu- la. The patients regained immediate kidney allograft func- tion and euglycemia with insulin-independence. Four pa- tients survived over one year. Episodes of acute rejection were observed in 4 patients, 3 of whom showed reversion after treatment of OKT3 or insulin. Early postoperative complications included peritoneal infection ( 2 patients ), wound infection (2) and renal hematoma (1). CONCLUSION: ED-SPK without Roux-en-Y anastomosis is safe and preferable to the patients with IDDM associated with uremia.

关键词： pancreas kidney transplantation diabetes

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Protective effects of glycine pretreatment on brain-death donor liver

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Hepatobiliary & Pancreatic Diseases International 2005年第1期4卷 37-40页

作者： Shui-Jun Zhang, Ji-Hua Shi, Zhe Tang, Yang Wu and Shi Chen Zhengzhou, china Department of Surgery, First Affiliated Hospital of Zhengzhou university, Zhengzhou 450052, china institute of organ transplantation, tongji medical college , huazhong university of science and technology, wuhan 430030 , china Department of Surgery First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China. zhangshuijin@***

BACKGROUND: Morphological and functional changes commonly occur in livers of brain-death donors. Preven- tion of liver injury from brain-death will benefit the results of transplantation. This study was conducted to evaluate the protection effects of glycine on the liver of brain-death donor. METHODS: Fourty-two male Wistar rats were randomly divided into brain-death donor (BDD) group (B), glycine pretreatment group with BDD (G), and strychnine pre- treatment group with BDD(S). For these groups, brain death model was established in donor rats and liver trans- plantation was performed subsequently utilizing microsur- gical techniques. After the establishment of the model and during cold rinsing of liver donors or liver reperfusion of recipients, glycine was given at a dose of 0. 6 mmol, 25 μmol and 25 μmol in the group G, and a same dose of gly- cine and strychnine (1000 :1) was prescribed for the group S, but nothing for the group B. Before cold rinsing at 2 and 6 hours after portal vein(PV) reperfusion, blood sam- ples were taken from infrahepatic vena cava (IHVC) to de- termine the levels of alanine aminotransferase (ALT), as- partate aminotransferase (AST), tumor necrosis factor al- pha (TNF-α) and hyaluronic acid (HA). At 6 hours after PV reperfusion, graft samples were fixed for morphological observation and apoptosis of hepatocytes was detected using the TUNEL method. RESULTS: Before liver cold rinsing and at 2 and 6 hours af- ter PV reperfusion, the serum levels of ALT, AST, TNF-α, HA and apoptosis index (AI) in the groups B and S were significantly higher than those in the group G (P 0.05). Electron microscopy showed that Kupffer cells were activated and hepatic cells injured more obvious- ly in the groups B and S than in the group G. CONCLUSION: Glycine pretreatment can improve the via-bility of the liver of the brain-death donor rat.

关键词： rats liver transplantation brain death glycine Kupffer cells donor

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Panax notoginseng saponins preconditioning protects rat liver grafts from ischemia/reper- fusion injury via an antiapoptotic pathway

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Hepatobiliary & Pancreatic Diseases International 2005年第2期4卷 207-212页

作者： Yi Zhang, Qi-Fa Ye, Li Lu, Xian-Lin Xu, Ying-Zi Ming and Jian-Sheng Xiao wuhan, china institute of organ transplantation, tongji Hospital, tongji medical college, huazhong university of science and technology, wuhan 430030, china Xiangya transplantation medical Academy, Third Xiangya Hospital, Xiangya Medi- cal college, Central South university, Changsha 410013, china institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of primary graft dysfunction and renders an al- lograft more immunogenic in orthotopic liver transplanta- tion (OLT). Panax notoginseng saponins (PNS) has been re- ported to exert protective effects against I/R injury to vari- ous organs. The objective of this study is to investigate whether PNS preconditioning protects rat liver grafts from I/R injury via an antiapoptotic pathway. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation ( OLT) and were divided into PNS preconditioning group (group P) and normal saline control group (group N) randomly according to whether PNS (50 mg/kg) was injected intra- venously 1 hour before liver grafts harvesting, and sham group (group S). The animals were separately killed 2, 6 and 24 hours after reperfusion. Plasma samples were collect- ed for test of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Liver tissues were collected to de- tect histological changes, apoptosis and the expression of TNF-α, Bcl-2 and Caspase-3 mRNA. RESULTS: The serum levels of ALT and AST and the apop- tosis index (AI) of liver tissue in group P were lower than in group N significantly 2, 6 and 24 hours after reperfusion. Compared with group N, the expression of TNF-a and Caspase-3 mRNA was reduced significantly in group P 2 and 6 hours after reperfusion and the expression of Bcl-2 mRNA was enhanced significantly in group P 6 and 24 hours after reperfusion. CONCLUSIONS: PNS preconditioning protects liver grafts from I/R injury effectively in rat OLT via an antiapoptotic pathway. The antiapoptotic mechanisms of PNS may in- clude inhibiting the expression of TNF-a and Caspase-3 and enhancing the expression of Bcl-2.

关键词： Panax notoginseng saponins liver transplantation ischemia/reperfusion injury apoptosis

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Preconditioning effects on expression of proto-oncogenes c-fos and c-jun after hepatic ischemia/reperfusion in rats

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Hepatobiliary & Pancreatic Diseases International 2005年第2期4卷 197-202页

作者： Jian-Sheng Xiao, Fang-Gang Cai, Ying Niu, Yi Zhang, Xian-Ling Xu and Qi-Fa Ye wuhan, china Research institute of organ transplantation, tongji Hospital, tongji medical college, huazhong university of science and technology, wuhan 430030, china Department of General Surgery, First Affiliated Hospital, Fujian Medi- cal college, Fuzhou 350005, china and Xiangya medical Trans- plantation Academy of Central South university, Changsha 410013, china Research institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. super_xiaoj@***

BACKGROUND: Ischemia/reperfusion is the main cause of hepatic damage in liver transplantation. Immediate early genes (IEGs) encode proteins can regulate expression of cellular response genes after injury, and is associated with tissue repair and cell apoptosis. The purpose of this re- search was to investigate the effects of preconditioning on expression of immediate early genes c-fos and c-jun follow- ing hepatic ischemia/reperfusion (IR) and its roles in cellu- lar regeneration and apoptosis. METHODS: Ninety-six Wistar rats were randomly divided into IR group and hepatic ischemic preconditioning (IPC) group, and each group was further divided into eight sub- groups (n =6). The model of partial liver ischemia/reper- fusion was used. The rats were subjected to 60-minute liver ischemia, preceded by 10-minute preconditioning. After 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, 24-hour reperfusion, the se- rum and liver tissue in each group were collected to detect the level of serum ALT/AST, liver histopathology, expres- sion of c-fos, and c-jun mRNA. Flow cytometer was used to detect Ki67 and Sub-G1 as the quantity indicators of cell regeneration and apoptosis respectively. RESULTS: Compared with IR group, IPC group showed a significantly lower ALT/AST level in 0. 5-hour sub-group to 8-hour sub-group (P<0.05). Ki67 elevated significantly at 0.5, 1, 2 hours, but decreased significantly at 24 hours ( P < 0 . 05). Ap index decreased significantly after 1-hour reperfusion(P<0.05). Expressions of c-fos and c-jun mR- NA were low, especially c-jun at 0.5, 1 and 2 hours after reperfusion. CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, and this protec- tive effect may be related to influence transcription levels of c-fos and c-jun.

关键词： liver ischemic preconditioning immediate early genes c-fos c-jun

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抗白细胞介素6单克隆抗体治疗延长小鼠同种心脏移植物存活时间的实验研究

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华中科技大学学报（医学版） 2010年第2期39卷 197-201页

作者：雷钧何凡吴敏郑翔李舒媛陈知水华中科技大学同济医学院附属同济医院器官移植研究所器官移植教育部重点实验章器官移植卫生部重点实验室武汉430030

目的观察应用抗白细胞介素6(IL-6)单克隆抗体(anti-IL-6 monoclonal antibody,anti-IL-6 mAb)对同种异体小鼠心脏移植排斥反应的抑制作用,并探讨其可能的作用机制。方法建立小鼠颈部异位心脏移植模型。实验动物随机分为同系移植组、移... 详细信息

目的观察应用抗白细胞介素6(IL-6)单克隆抗体(anti-IL-6 monoclonal antibody,anti-IL-6 mAb)对同种异体小鼠心脏移植排斥反应的抑制作用,并探讨其可能的作用机制。方法建立小鼠颈部异位心脏移植模型。实验动物随机分为同系移植组、移植治疗组(每日注射3 g/L anti-IL-6 mAb 0.1 mL)和移植模型组(注射等量生理盐水)。ELISA法检测受鼠移植术后第3、6天外周血IL-6的表达水平,观察各组移植心脏存活时间,病理分析检测排斥反应程度,流式细胞术(FCM)检测各组受鼠脾脏及移植心脏中CD4+CD25+调节性T细胞比例变化,RT-PCR检测移植心脏IL-6I、FN-γI、L-17、RORγt和Foxp3 mRNA的表达水平。结果①治疗组外周血IL-6表达水平较模型组明显降低(P<0.01);②治疗组移植心脏存活时间较模型组明显延长[(22.0±2.3)d vs(7.7±0.8)d,P<0.01],排斥反应病理分级明显下降(Stanford 2级);③治疗组移植心脏中IFN-γI、L-6I、L-17和RORγt mRNA表达水平较模型组显著下降(均P<0.05),脾脏及移植心脏中浸润的CD4+CD25+调节性T细胞比例及Foxp3 mRNA表达水平均明显升高,与模型组比较差异有统计学意义(均P<0.05)。结论anti-IL-6 mAb治疗可抑制Th1、Th17型细胞因子的分泌,促进CD4+CD25+Foxp3+T细胞产生,抑制单个核细胞浸润并有效延长小鼠同种移植心脏的存活时间。

关键词：心脏移植急性排斥反应白细胞介素6 单克隆抗体

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移植肾间隔室综合征的临床诊断与防治

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华中科技大学学报（医学版） 2010年第2期39卷 266-268页

作者：昌盛周平林正斌张伟杰曾凡军明长生陈知水陈孝平华中科技大学同济医学院附属同济医院器官移植研究所武汉430030

目的探讨移植肾间隔室综合征的临床诊断与防治。方法收集华中科技大学同济医学院附属同济医院器官移植研究所2004年7月至2008年4月肾移植术后发生移植肾间隔室综合征的17例病例,回顾分析其发生影响因素、临床特点及治疗措施。结果17例... 详细信息

目的探讨移植肾间隔室综合征的临床诊断与防治。方法收集华中科技大学同济医学院附属同济医院器官移植研究所2004年7月至2008年4月肾移植术后发生移植肾间隔室综合征的17例病例,回顾分析其发生影响因素、临床特点及治疗措施。结果17例患者均因移植肾周压力升高,压迫移植物而出现尿量减少以至无尿。其中1例发生移植肾动脉栓塞而被迫切除移植肾;3例经积极针对病因处理,移植肾压力降低后肾功能迅速恢复;余13例经5~18次血透后,肾功能均逐渐恢复正常。结论移植肾间隔室综合征作为移植肾功能恢复延迟的一种特殊类型并不罕见,可影响患者恢复。对高危人群早期诊断、及早针对病因进行治疗是有效减少此类并发症的关键。

关键词：移植肾间隔室综合征移植肾功能恢复延迟肾移植

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雌激素对天然杀伤细胞的作用

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现代免疫学 2006年第3期26卷 247-250页

作者：闫冀焕周鸿敏王雪琼周绍棠陈忠华华中科技大学同济医学院附属同济医院器官移植研究所国家教育部器官移植重点实验室国家卫生部器官移植重点实验室华中科技大学同济医学院附属同济医院器官移植研究所国家教育部器官移植重点实验室国家卫生部器官移植重点实验室武汉430030

为探讨雌激素对NK细胞的作用,在不同时间把不同剂量的雌激素加入培养体系中,分析雌激素对无和有外来刺激原刺激NK细胞的影响。结果显示培养开始加入生理剂量、低于生理剂量和超生理剂量的雌激素均可明显抑制NK细胞的增殖;培养48 h后加... 详细信息

为探讨雌激素对NK细胞的作用,在不同时间把不同剂量的雌激素加入培养体系中,分析雌激素对无和有外来刺激原刺激NK细胞的影响。结果显示培养开始加入生理剂量、低于生理剂量和超生理剂量的雌激素均可明显抑制NK细胞的增殖;培养48 h后加入相同剂量的雌激素,生理剂量和低于生理剂量雌激素仍可明显抑制NK细胞的增殖,超生理剂量雌激素非但不能抑制反而使NK细胞的数量增加。

关键词：雌激素天然杀伤细胞

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