胰腺、肾脏在单独和联合移植中排斥反应的差异

目的 比较胰腺、肾脏在单独和联合移植中排斥反应的差异。方法 在大鼠同种异体单独胰腺移植、单独肾脏移植和肺肾联合移植基础上,对胰腺、肾脏在单独和联合移植中的排斥瓜反应分别进行了比较。结果 （１）胰腺在联合肾脏移植中受到肾脏保护,与单独上比,功能与形态不者到显著改观;（２）肾脏在联合胰腺移植时未受到胰腺保护,与单独移植比较,各项指标未得到显著改善。结论 胰腺与肾脏联合移植的结局优于单独胰腺移植,而肾脏     

肝肾联合移植中肝脏对肾脏的保护作用

目的探讨肝肾联合移植中肝脏对肾脏的保护作用。方法回顾性分析2001年10月至2006年6月18例接受肝肾联合移植患者的资料,并以同一供体的对侧肾脏所完成的单独肾移植18例受者作为对照,2组患者年龄、性别、血型、冷热缺血时间、人类白细胞抗原（HLA）配型、肾病原发病、免疫抑制方案等条件基本匹配。对2组患者间移植肾急性排斥反应（AR）、慢性排斥反应（CR）、移植肾功能延迟恢复（DGF）的发生率以及出院时血肌酐（SCr）水平进行比较。结果肝肾联合移植组AR和DGF发生率均明显低于单独肾移植组,差异有统计学意义（5．6％对33．3％,P= 0．044;0对27．8％,P=0．023）;肝肾移植组CR发生率明显低于单独肾移植组,但差异无统计学意义（0对11．1％,P=0．243）。出院时平均SCr水平肝肾移植组明显低于单独肾移植组,差异有统计学意义[（57．1±6．0）μmol／L对（123．0±11．7）μmol／L,P=0．018）]。结论肝肾联合移植中肝脏对肾脏具有保护作用,能够维持良好的移植肾功能。     

子鼠胰腺干细胞与胰岛联合移植治疗糖尿病

目的 探讨利用子鼠胰腺干细胞与胰岛联合移植保护移植胰岛,提高糖尿病移植疗效的可行性.方法 分离纯化孕16 d SD大鼠子鼠:胰腺干细胞培养传代,行Nestin免疫组织化学及流式细胞术鉴定;分离纯化SD大鼠胰岛,分联合移植组(10只)、单独移植组(10只)及正常对照组(10只),分别将2×105个子鼠:胰腺干细胞与800个胰岛和单纯800个胰岛移植至糖尿病大鼠模型左肾包膜下,定期监测各组大鼠血糖情况及留取血浆ELISA测胰岛素含量,观察胰岛存活时间.结果 子鼠:胰腺干细胞培养传代3代后细胞涂片免疫组织化学示存在Nestin阳性细胞,流式细胞术测定nestin阳性细胞含量占74.1%.联合移植组大鼠均于术后第3天起血糖开始下降,血浆胰岛素水平逐渐升高,术后5 d内血糖可降至正常[(5.4±0.6)mmol/L],血浆胰岛素达到正常水平[(509.8±16.6)ng/L],胰岛存活时间(18.2±2.4)d;单独移植组大鼠血糖可于术后1周内降至正常[(6.1±0.9)mmol/L],胰岛存活时间(14.4±2.1)d;两组胰岛存活时间差别有统计学意义(P《0.05).结论 子鼠胰腺干细胞与胰岛联合移植可保护胰岛功能,延长胰岛体内存活时间,提高移植疗效.     

肝、胰Ⅰ期联合移植治疗合并糖尿病的良性终末期肝病一例

目的 对1例原位肝、异位胰腺I期联合移植进行总结.方法 对1例终末期肝病合并2型糖尿病的患者施行肝、胰I期联合移植,肝脏为原位移植,胰腺异位移植于右侧髂窝,胰液空肠引流.术后采用他克莫司、霉酚酸酯及糖皮质激素预防排斥反应,并辅以两剂达利珠单抗.结果 术后移植胰腺功能良好,第2天即停用胰岛素.术后14 d,移植肝出现轻度急性排斥反应,调整他克莫司的用量后逆转.受者已存活15个月,移植肝脏及胰腺功能均正常.结论 肝、胰联合移植是治疗终末期肝病合并糖尿病的有效方法.     

当今胰腺移植的重大进展与前景

胰腺移植主要包括单独胰腺移植 ( pancreastransplantationalone,PTA )、肾移植后胰腺移植 ( pancreasafterkidneytransplantation ,PAK )和胰肾联合移植 (simultaneouspancreas kidneytransplantation ,SPK)。与其它实体大器官移植一样 ,胰腺移植成功的真正转折始于 2 0世纪 70年代末。随着新型免疫抑制剂的开发和应用、器官保存技术的改进和外科技术的日臻成熟 ,胰腺移植在全球范围内得到迅猛开展 ,胰腺移植受体及器官存活率显著提高。据国际胰腺移植登记中心(InternationalPancreasTransplantRegistry ,IPTR )记录 ,至2 0 0 1年 1…     

胰腺移植后巨细胞病毒感染的流行病学调查

CMV感染是胰腺移植后常见并发症且发病率和死亡率均较高。目前对于胰腺移植后CMV感染的流行病学研究并不全面，较多的报道集中在胰肾联合移植，鲜有肾移植后胰腺移植和单独胰腺移植的文献。鉴于此，美国和中国学者共同就3种类型胰腺移植后CMV感染患者的临床特征、发病率、危险因素、CMV感染情况和转归进行了分析。     

大鼠肝小肠联合移植的研究

采用封闭群大鼠建立一种肝小肠联合移植模型，研究肝移植后的自然耐受状态对小肠移植物的保护作用。结果发现：在封闭群单独小肠移植组大鼠，术后１４天内排斥率为１００％。     

接受同一供体肝肾联合移植与肾移植的临床研究

目的探讨肝肾联合移植肝脏对肾脏的保护作用。方法我院移植中心2002年5月至2006年9月间共进行8例肝肾联合移植手术，对此8例患者及接受同一供体对侧供肾8例肾移植患者及移植物存活率、排斥反应发生率进行分析。结果肝肾联合移植患者及移植物存活率为100％，无可证实排斥反应发生。术后8例患者移植肝功能迅速恢复正常，7例移植肾功能迅速恢复正常，1例移植肾发生急性肾小管坏死，于术后第52天肾功能恢复正常。对应8例单纯肾移植患者，发生急性排斥反应1例，予甲基强的松龙冲击治疗及应用抗人T淋巴细胞免疫球蛋白（anti-thymocyte globulin，ATG）后，于术后50d移植肾功能恢复正常，余7例患者恢复良好，至末次随访肾功能均正常。结论肝肾联合移植肝脏对肾脏有一定的保护作用。     

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肝脏作为单独实质器官进行移植 ,习称肝脏移植。但有时肝脏与另一生命器官如肾、小肠、心同时移植给一个受者 ,则统称联合移植。1　肝脏单独移植现今 ,临床肝移植在先进国家的大型综合性医院来说 ,已是一个常规手术 ,其技术难度极大 ,但已经成熟 ,处于推广阶段。据世界移植中心登记名录 (ＷＴＣＤ)统计 ,自 2 0世纪 90年代以来 ,每年以 6 0 0 0～70 0 0例速度递增 ,作为单一脏器移植 ,累积总数到 1997年底为 6 2 5 6 2例 ,而 1998年底已达 72 311例 ,1年内增加近万例 ,速度显然加快。在我国这个趋势更是明显 ,我国大陆到1998年底 ,全国已…     

病毒性肝炎患者行肝脏移植

对病毒性肝炎肝功衰竭患者行肝脏移植 ,术后病毒性肝炎复发是影响生存率的主要因素 ,尤其体内有病毒复制的活动性肝炎患者复发率更高。因此被认为是肝脏移植的相对禁忌证。肝炎复发的原因是患者手术时在肝外有病毒复制 ,故单独行肝移植并不能完全清除体内病毒 ;移植后采用免疫抑制剂又进一步促进了病毒的生长。但是近来随着对病毒性肝炎发病机制认识的加深和新型抗病毒药物的不断问世 ,复发率得到了良好的控制 ,欧洲 17个移植中心对 372例肝炎进行肝移植后的一项联合调查中发现 ,334例随访患者生存率 1年为75 % ,3年为 6 3%。其中乙型肝炎复…     

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.     

Serum immunoreactive anodal trypsinogen and urinary amylase as biochemical markers for rejection of clinical whole-organ pancreas allografts having exocrine drainage into the urinary bladder.

Rejection of pancreas allografts is best measured today by co-monitoring the creatinine of a simultaneously transplanted kidney allograft from the same donor. This methodology discourages pancreas transplantation for patients who have previously received a kidney allograft and preuremic patients. Thus, an early, graft-specific marker of rejection is desirable. In this study we compared 2 putative biochemical markers for rejection of pancreas allografts, serum immunoreactive anodal trypsinogen and urinary amylase, with serum creatinine in 15 simultaneously transplanted type I diabetics. Serial values during hospitalizations were determined. Follow-up ranged from 18 to 134 postoperative days. Rejection was diagnosed clinically and considered real if the patient received a course of anti-rejection medication. Ten of these 15 patients experienced a total of 21 rejection episodes. For all episodes of rejection, serum trypsinogen rose from a baseline of 398.1 +/- 25 ng/ml to 1686.2 +/- 317.9 ng/ml (P less than 0.001) on the day of rejection. Urinary amylase fell from 88,310 +/- 7877 U/24 hr to 37,508 +/- 7142 U/24 hr (P less than 0.001). For 10 patients in whom rejection was diagnosed on the initial hospitalization so that serial prediagnosis sera and urines were available, anodal trypsinogen rose from a baseline of 756 +/- 263 ng/ml to 1936 +/- 582 ng/ml (P less than 0.001). Urinary amylase values for these same 10 patients did not change significantly (baseline = 55,788 +/- 18,404 U/24 hr, rejection = 47,133 +/- 14,737 U/24 hr, (P = 0.7). We conclude that serum anodal trypsinogen behaves as a graft-specific biochemical marker for rejection of vascularized pancreas allografts.     

脾脏在小鼠同种肝移植排斥反应中的作用

目的 观察脾切除在小鼠同种肝移植急性排斥反应过程中的作用.方法 双袖套法建立小鼠原位肝移植模型,随机分为3组,即建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组,各组于移植术后14 d处死,ELESA法测定血清IgM水平;肝功能检测采用速率法;流式细胞仪检测CD4与CD8T细胞亚群;并同时行肝脏及脾脏的病理形态观察.结果 建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组血清IgM水平分别为3.0181±0.4627、3.0936±0.4559、3.1953±0.4449,各组间差异无统计学意义(P＞0.05);ALT水平分别为108.6875±20.3657、83.0000±22.7799、76.8000±19.5784,差异有统计学意义(P＜0.05);AST水平分别为:105.3750±29.0583、93.0000±22.7799、93.2000±33.4220,各组间差异无统计学意义(P＞0.05);CD46+/CD8+T细胞分别为:1.9162±0.2778、1.5654±0.4750、1.4616±0.2762,差异有统计学意义(P＞0.05);3组肝脏间质及汇管区淋巴细胞浸润程度依次减弱,供肝灶状坏死程度逐渐减轻,在保留脾脏组中建模后第14天脾脏边缘区及淋巴鞘较建模同时切除的脾脏增宽.结论 在小鼠同种异体肝移植排斥反应中细胞免疫起主要作用,脾切除可部分抑制同种异体肝移植急性排斥反应,保护供体肝脏.     

Contractile dysfunction in experimental cardiac allograft rejection: role of the poly (ADP-ribose) polymerase pathway.

Recent studies suggested that the peroxynitrite-poly (ADP-ribose) polymerase (PARP) pathway is activated during acute allograft rejection. We investigated whether PARP inhibition improves transplant function during cardiac rejection. Isogeneic Lewis-to-Lewis and allogeneic Dark Agouti-to-Lewis rat cardiac transplants were studied under treatment with placebo or with the PARP-inhibitor INO-1001 (1 mk/kg/day), Functional, biochemical and histological analysis were performed 3 and 5 days after transplantation. After 3 days, baseline left ventricular pressure-volume relationships did not differ between the groups. However, coronary blood flow (4.3 +/- 0.5 vs. 2.2 +/- 0.2 vs. 4.1 +/- 0.3 ml/min/g, P < 0.05) and contractile response to dobutamine (Delta+dP/dt: 98 +/- 11 vs. 57 +/- 7 vs. 88 +/- 8%, P < 0.05) decreased significantly in the placebo group, which was abolished by INO-1001. Vasodilatory response to acethylcholine was reduced in the placebo group (78 +/- 6 vs. 36 +/- 9 vs. 72 +/- 7%, P < 0.05). After 5 days, baseline systolic and diastolic pressure-volume relationships were impaired (P < 0.05) in the placebo group and the response to dobutamine and to acethylcholine deteriorated further which was abolished by INO-1001. Histology confirmed mild to moderate rejection after 3 days and severe acute rejection after 5 days in the allogeneic groups. Thus, contractile and vasomotor dysfunction occur in a typical time dependent manner during cardiac rejection, which can be reduced by PARP-inhibition.     

Effects of liver transplantation on the nutritional status of patients with cystic fibrosis.

The long-term effects of liver transplantation on nutritional status, body composition and pulmonary function in patients with liver disease associated with cystic fibrosis (CF) are poorly defined. We studied 15 patients with CF-associated biliary cirrhosis and severe portal hypertension. Seven underwent liver transplantation (age: 14.8 +/- 6.2 years), and eight were treated conservatively (age: 15.9 +/- 6.7 years). All patients were evaluated at baseline and thereafter yearly for a median duration of 5 years. During follow-up, transplanted patients gained weight and showed a significant increment in body mass index (P < 0.004), whereas patients without transplantation remained stable (P = 0.063). Baseline bone mineral content (dual energy X-ray absorptiometry scan) was lower than normal in all patients (more in transplanted patients) and increased in transplanted patients (P < 0.05), but not in patients without transplantation. In both groups percent body fat did not change, whereas fat free mass increased only in the transplant group (P = 0.06) (P < 0.03 versus nontransplanted patients). Only in transplanted patients' plasma concentrations of vitamin E and A increased (P < 0.05 versus nontransplanted patients). Forced espiratory volume in 1 s and forced vital capacity showed similar deterioration in transplanted and in nontransplanted patients. Liver transplantation is associated with long-term beneficial effects on the nutritional status of CF patients and seems to favor bone mineralization.     

The angiotensin II type 1 receptor blocker candesartan attenuates graft vasculopathy

OBJECTIVE: Transplant arteriosclerosis remains the major cause of graft failure after cardiac transplantation, although recent progress in immunosuppressive therapy has dramatically improved short-term survival of recipient. We investigated the effects of the angiotensin II type 1 receptor (AT(1)R) blocker candesartan on the development of transplant arteriosclerosis in a murine model of cardiac transplantation. MATERIALS AND METHODS: Hearts from DBA/2 (H-2(d)) mice were heterotopically transplanted into B10.D2 (H-2(d)) mice. Recipients were treated with oral administration of candesartan (1 mg/kg per day) or vehicle. Allografts were analyzed at 14 or 30 days after transplantation. RESULTS: Candesartan significantly reduced the development of coronary arteriosclerosis (intima/media ratio: 0.86 +/- 0.09 versus 0.57 +/- 0.10, P < 0.05), without affecting the degree of parenchymal rejection at 30 days. There was no significant difference in the expression of adhesion molecules and cytokines at 14 days. Candesartan significantly reduced the number of peripheral mononuclear cells that differentiated into smooth muscle-like cells in the presence of basic fibroblast growth factor and platelet-derived growth factor BB (27.1 +/- 3.1 versus 17.3 +/- 1.8 cells/HPF, P < 0.05). CONCLUSIONS: Angiotensin II may play a role in the pathogenesis of transplant arteriosclerosis. Blockade of AT(1)R might be effective as a prophylactic therapy for transplant arteriosclerosis along with conventional immunosuppressive drugs.     

肝联合其他器官移植术后近期免疫抑制策略的方案探讨

目的探讨肝联合其他器官移植术后近期的免疫抑制策略。方法我中心于2004年至2009年共实施肝联合其他器官移植22例,其中肝肾联合移植17例,肝胰十二指肠联合移植5例。存活时间大于3个月的患者共18例,比较此类患者与单一器官移植患者术后近期排斥反应发生率和免疫抑制策略的差别。结果肝联合其他器官移植的患者术后3个月内,移植肝排斥反应发生率为5．5％;移植肾的排斥反应发生率为5．9％;其他器官没有发生排斥反应,较我中心单一器官移植排斥反应发生率低。同时,肝联合其他器官移植患者免疫抑制剂初始剂量及术后近期所需浓度均较单一器官移植低。结论肝联合其他器官移植的患者,由于移植肝对其他移植器官的免疫保护作用,排斥反应发生率低,所需免疫抑制剂初始剂量及浓度均低于单一器官移植。但肝脏对其他移植器官的免疫保护作用机制尚需进一步研究。     

外用环孢素A联合CTLA4Ig延长异体移植鼠耳存活的研究

目的　探讨局部外用环孢素 A(Cs A)联合细胞毒性淋巴细胞相关抗原 4融合蛋白 (CTL A4 Ig)对异体复合组织移植的免疫抑制及诱导免疫耐受的作用。方法　建立吻合血管的同种异体大鼠耳廓移植模型 ,术后在移植耳皮肤表面外涂 Cs A并联合 CTL A4 Ig腹腔注射治疗 ,观察移植物的排斥反应及存活时间 ,检测移植后受体血清白细胞介素 - 2 (IL- 2 )含量变化。结果　对照组平均存活时间为 (7.8± 1.7)天 ;单纯用 Cs A治疗组为 (15 .2± 1.9)天 ,单纯CTL A4 Ig治疗组为 (16 .6± 2 .1)天 ;Cs A +CTL A4 Ig联合治疗组为 (2 8.8± 3.5 )天 ,与其它各组相比均有统计学意义 (P<0 .0 1) ;且联合治疗组的受体血清 IL - 2含量最低 ,尤以第 5、7天为著 ,与其它各组相比有统计学意义 (P<0 .0 1)。结论　局部外用 Cs A联合 CTL A4 Ig能有效抑制异体复合组织移植排斥反应 ,显著延长移植物存活时间。     

Differential response of kidney and pancreas rejection to cyclosporine immunosuppression.

Immunological interferences between kidney and pancreas transplants were investigated in a genetically defined rat model of combined kidney and pancreas transplantation. Kidney and whole-pancreas grafts were transplanted microsurgically either as individual grafts or in a combined technique. Whole pancreas grafts were grafted into streptozotocin diabetic recipients (55 mg/kg bodyweight i.v.) three days after induction of diabetes. The exocrine secretion was suppressed by duct ligation. Rejection of the grafts was defined by recurrence of diabetes in pancreas-grafted recipients and renal failure after kidney transplantation. There were marked differences in the efficacy of identical short-term cyclosporine immunosuppression (15 mg/kg intramuscularly for 14 days): DA kidneys survived indefinitely in LEW rats (MST greater than 100 days), while DA pancreas allografts underwent prolonged but not permanent survival (P less than 0.01) either as individual grafts (MST 27.3 +/- 1,9 days) or when transplanted simultaneously together with the kidney (44 +/- 16 days) (P less than 0.01). LEW rats carrying a DA kidney for 100 days also rejected a subsequent donor-specific pancreas transplant within 30 days. The histological alterations in the kidney were more pronounced than after cyclosporine-induced DA kidney long-term survival alone. By contrast to the rejecting subsequently transferred pancreas, a metachronous second DA kidney was permanently accepted (greater than 100 days) without further immunosuppression after removal of the first graft, while unrelated LEW. 1U kidneys were acutely rejected. In summary, the results indicate that there are not only quantitative differences of kidney and pancreas allograft survival but also differences concerning the state of immunological unresponsiveness induced by identical cyclosporine immunosuppression. While CsA induces donor-specific immunological unresponsiveness after kidney transplantation, pancreas transplants are all eventually rejected after some differential prolongation of survival. Further investigations on the effects of different MHC and minor alloantigens may provide more insight into the complex immunological situation of individual and combined kidney and pancreas transplantation.     

Fas配体表达对同种胰岛移植的影响

目的探究睾丸细胞FasL表达能否对共移植的胰岛移植物提供免疫豁免作用以及胰岛细胞FasL基因转染对同种胰岛移植的影响.方法将同种大鼠胰岛及睾丸细胞同时移植于糖尿病受体,重组腺病毒AdV-FasL感染胰岛细胞后移植,观察移植物存活情况、胰岛功能,并检测移植物内浸润淋巴细胞以及基因转染胰岛细胞凋亡情况.结果单纯移植胰岛组平均存活期为(6.3±0.56)?d.与胰岛细胞同时移植的睾丸细胞数增加至1×107时,存活期大于50?d(P＜0.05).表达FasL的睾丸细胞在移植物内诱导浸润淋巴细胞凋亡.FasL基因转染组出现排斥加速,存活期缩短至(3.4±0.24)?d.FasL转染的胰岛细胞在移植后24h见FasL表达,48h表达增强,移植后FasL转染胰岛细胞凋亡.结论表达FasL的睾丸细胞与胰岛同时移植可诱导活化的淋巴细胞凋亡,使胰岛移植物获得免疫豁免、存活期延长,但通过FasL基因转染使胰岛细胞直接表达FasL引起胰岛细胞凋亡和粒细胞浸润,导致排斥加速.