甘露醇对大鼠小肠移植缺血再灌注损伤的保护作用

目的:探讨甘露醇对大鼠小肠移植缺血再灌注(ischemia and reperfusion,I/R)损伤的保护作用及其作用机制.方法:建立大鼠小肠移植I/R损伤模型.雄性SD大鼠随机分为假手术组、I/R组和甘露醇处理组.对I/R损伤后不同时间(0.5,1,1.5 h)的小肠标本进行组织病理学观察并检测小肠组织中超氧化物歧化酶(SOD,U/mgprot)和丙二醛(MDA,nmol/mgprot)的含量.结果:不同时间点I/R组小肠绒毛高度和黏膜厚度低于假手术组(P<0.01)和甘露醇处理组(P<0.05).不同时间点I/R组(16.24±4.56,18.50±2.89.19.42±2.21)MDA水平高于假手术组(10.26±1.72,P<0.01)和甘露醇处理组(11.24±1.51,14.03±3.12,16.06±3.62;P<0.05);而SOD水平低于假手术组和甘露醇处理组(398.36±18.81,363.16±16.29,325.66±14.58 vs 447.97±16.94;422.30±17.41,385.09±19.11,346.15±14.10;P<0.01或P<0.05).结论:甘露醇可通过清除氧自由基的方式对移植小肠缺血再灌注损伤起到保护作用.     

Formation of microchimerism in rat small bowel transplantation by splenocyte infusion

AIM: To investigate the effect of donor splenocyte infusion combined with cyclosporine A (CsA) on rejection of rat small bowel transplantation (SBT). METHODS: Male Sprague-Dawley (SD) rats and female Wistar rats weighing 230-270 g were used as donors and recipients respectively in the study. Heterotopic small bowel transplantation was performed. The rats were divided into three groups: group one receiving allotransplantation (SD rarr Wistar), group two receiving allotransplantation (SD rarr Wistar) + donor splenocyte infusion, group three receiving allotransplantation (SD rarr Wistar) + donor splenocyte infusion + CsA followed by CsA 10 mg/kg per day after transplantation, in which recipient Wistar rats were injected with 2 x 10(8) SD splenocytes 28 d before transplantation, and treated with CsA after transplantation. Finally, the specific DNA fragment of donor Y chromosome was detected in recipient peripheral blood and skin by PCR. The survival time after small bowel transplantation was observed. Gross and histopathological examinations were performed. RESULTS: The survival time after small bowel trans-plantation was 7.1 +/- 1.2 d in group 1, 18.4 +/- 3.6 d in group 2 and 31.5 +/- 3.1 d in group 3. The survival time was significant longer (P < 0.01) in group 3 than in groups 1 and 2. The gross and histopathological examination showed that the rejection degree in group 3 was lower than that in groups 1 and 2. CONCLUSION: Donor splenocyte infusion combined with CsA decreases remarkably the rejection and prolongs the survival time after rat small bowel transplantation.     

Formation of microchimerism in rat small bowel transplantation by spienocyte infusion

AIM: To investigate the effect of donor splenocyte infusion combined with cyclosporine A (CsA) on rejection of rat small bowel transplantation (SBT). METHODS: Male Sprague-Dawley (SD) rats and female Wistar rats weighing 230-270 g were used as donors and recipients respectively in the study. Heterotopic small bowel transplantation was performed. The rats were divided into three groups: group one receiving allotransplantation (SD→Wistar), group two receiving allotransplantation (SD→Wistar) donor splenocyte infusion, group three receiving allotransplantation (SD→Wistar) donor splenocyte infusion CsA followed by CsA 10 mg/kg per day after transplantation, in which recipient Wistar rats were injected with 2×108 SD splenocytes 28 d before transplantation, and treated with CsA after transplantation. Finally, the specific DNA fragment of donor Y chromosome was detected in recipient peripheral blood and skin by PCR. The survival time after small bowel transplantation was observed. Gross and histopathological examinations were performed. RESULTS: The survival time after small bowel transplantation was 7.1±1.2 d in group 1, 18.4±3.6 d in group 2 and 31.5±3.1 d in group 3. The survival time was significant longer (P < 0.01) in group 3 than in groups 1 and 2. The gross and histopathological examination showed that the rejection degree in group 3 was lower than that in groups 1 and 2. CONCLUSION: Donor splenocyte infusion combined with CsA decreases remarkably the rejection and prolongs the survival time after rat small bowel transplantation.     

异氟醚预处理对心肌缺血再灌注损伤的保护作用

目的:观察异氟醚预处理对体外循环心内直视手术心肌的保护作用。方法:20例瓣膜置换术患者(ASA 2～3 级),随机分为预处理组(Ⅰ组)和对照组(C组)。分别于麻醉后(T_1),主动脉开放后15分钟(T_2)、2小时(T_3)、24小时(T_4)时间点取血样,检测血清CGRP、ET、cTnI;另于术前、术后第1、3天记录同步12导联心电图.测定其QTd和 QTcd。结果:主动脉开放后,CGRP含量在两组患者24小时之内都有显著增加(P<0.01),T_2时,预处理组的CGRP水平明显高于对照组的(P<0.05);ET在T_2时两组都有显著上升(P<0.01),但预处理组的上升幅度明显低于对照组(P<0.05);T3、T4时,对照组cTnI水平显著高于预处理组;术后两组QTd和 QTcd显著增加(P<0.01),其中对照组的增加较多,且第1天明显多于预处理组(P<0.05);结论:异氟醚预处理能减少心肌的缺血再灌注损伤,降低术后心律失常发生率,有利体外循环后心功能恢复。     

缺血预处理对大鼠脑缺血再灌注损伤神经细胞的保护作用

目的探讨大鼠局灶性脑缺血预处理对脑缺血再灌注损伤后神经元的保护作用。方法健康雄性SD大鼠60只,随机分为3组:假手术组、大脑中动脉缺血再灌注(MCAO)组、预处理(BIP)组,每组按照再灌注后12 h、1、2、3 d四个时间点平均分为4个亚组,制备缺血预处理模型,分别用流式细胞术和ELISA法观察脑缺血预处理对缺血再灌注大鼠缺血半暗带神经细胞凋亡率及血清神经元特异性烯醇化酶(NSE)含量的影响。结果大鼠脑缺血再灌注后12 h,MCAO组细胞凋亡发生率及血清中NSE的含量较假手术组显著增加(P<0.01),1 d时达到高峰,以后时间点逐渐下降,但仍高于假手术组(P<0.01);BIP组各个时间点神经元凋亡发生率及血清NSE较MCAO组显著降低(P<0.05,P<0.01)。结论大鼠局灶性脑缺血预处理对脑缺血再灌注神经元损伤有保护作用。     

亲体小肠移植术后并发症的内镜与病理监测

目的探讨亲体小肠移植术后并发症的发生情况与防治。方法实施1例母亲为供体的小肠移植。通过内镜与病理检查对移植小肠并发症进行监测。结果移植手术过程顺利，受体生命体征稳定。术后第37天内镜和活检病理发现急性排斥反应，术后第65天活检病理发现巨细胞病毒感染。经激素冲击、OKT3抗排斥治疗，结合抗病毒治疗，病情得到控制，至发稿时已存活18个月。结论小肠移植患者容易发生急性排斥反应和感染等并发症，加强监护和采用内镜活检及病理检查可以及时发现隐匿的病情，控制病情，提高存活率。     

小鼠小肠移植血管吻合技术的改进

目的　改进血管吻合技术,提高小鼠小肠移植血管吻合的成功率。方法　BAL B/ c小鼠小肠移植模型6 0例,每组2 0例,分别采用改良连续缝合方法(A组)、间断缝合方法(B组)及每针均收紧的连续缝合方法(C组) ,将小鼠供体腹主动脉和门静脉分别与受体腹主动脉和下腔静脉行端侧吻合。结果　三组总手术时间:A组(15 2±4 6 )分钟,B组(190±5 1)分钟,C组(183±38)分钟,A组与B、C两组相比,P <0 .0 5 ,差异有显著性。血管并发症:A组5例(2 5 % ) ,B组13例(6 5 % ) ,C组12例(6 0 % ) ,A组与B、C两组相比,P <0 .0 5 ,差异有显著性。总手术成功2 6例(43.3% ) ,其中A组13例(6 5 % ) ,B组6例(30 % ) ,C组7例(35 % ) ,A组与B、C两组相比,P<0 .0 5 ,差异有显著性。结论　改良连续血管吻合方法手术时间短,血管并发症少,手术成功率高。     

左旋精氨酸对缺血-再灌注损伤肝脏的保护作用

目的：探讨左旋精氨酸（L-arginine,L-Arg）对肝缺血－再灌注损伤（hepatic ischemia-reperfusion injury,HIRI）的防治作用及其机理。方法：选择HIRI家兔及肝手术患者,观察一氧化氮水平、丙二醛浓度、血栓素B2和6－酮基－前列腺素F1α含量、血栓素B2/6－酮基－前列腺素F1α比值、ALT活性、肝细胞形态学的变化及L-Arg对上述指标的影响。结果：HIRI期间,NO、6－酮基－前列腺素F1α显著下降,MDA、血栓素B2、血栓素B2/6-酮基-前列腺素F1α及ALT明显升高,肝细胞形态学发生异常变化;使用L-Arg后,上述指标的异常变化显著减轻,其差异有显著意义（Ｐ＜0.05和Ｐ＜0.01＝。 结论：L－Arg通过提高机体NO水平、降低MDA含量及纠正血栓烷 A2与PGI2的平衡,对HIRI有积极的防治作用。     

大鼠肝肠联合移植后肝对小肠的免疫保护作用

目的：建立大鼠肝肠联合整体移植模型,研究移植肝是否对移植小肠具有免疫保护作用．方法：选用封闭群SD大鼠和近交系Wistar大鼠．实验分5组：同基因小肠移植组、同基因肝移植组、异基因小肠移植组、异基因肝移植组、肝肠联合移植组．同基因移植供受体均为Wistar大鼠,异基因小肠移植、肝移植和肝肠联合移植供受体分别选用SD和Wistar大鼠．肝肠联合移植在切取移植物后,利用供体胸段下腔静脉在门静脉侧壁建立一袖套,并安置套管．受体手术时,将此门静脉侧壁袖套与受体门静脉残端套管法吻合．供体肠系膜上动脉与受体右肾动脉吻合．免疫保护作用通过术后5,7,14 d从各组随机取出4只大鼠的移植物普通病理检查及细胞凋亡检测评估．结果：肝肠联合移植模型建立手术成功率73．3%(22/30)．同基因移植组术后仅表现为缺血-再灌注损伤所致的轻度组织损伤及炎症反应,移植物细胞凋亡数逐渐减少．异基因移植术后均出现急性排斥、移植物细胞凋亡数递增,并且较同基因移植多,差别有显著性．小肠移植术后5,7,14 d分别表现为轻度、中度和重度排斥．而肝肠联合移植的小肠移植物术后5,7,14 d分别表现为轻度、轻度和中度排斥,且14 d时小肠细胞凋亡数较异基因小肠移植组少,差别具有显著性(16．9±4．3 vs 20．5±6．3,P＜0．05)．术后各时间点异基因肝移植和肝肠联合移植的移植肝排斥反应严重程度相同,细胞凋亡数比较无显著差异．结论：此法建立大鼠肝肠联合移植模型可行．肝肠联合移植时肝对小肠具有免役保护作用．     

Capsule enteroscopy in small bowel transplantation

BACKGROUND: Enteroscopy plays a key role in the post-operative monitoring of patients with small bowel transplantation for the early detection of post-transplant complications and for the assessment of the graft's integrity. Routine surveillance enteroscopies (trans-stomal terminal ileoscopy or jejunoscopy) are invasive, may be unsafe in frail patients, and only allow incomplete exploration of the transplanted graft, which may be unsatisfactory. since the distribution of the lesions is often patchy or segmental. AIMS. To evaluate the potential of capsule enteroscopy, a new, minimally invasive technique which allows complete exploration of the small bowel. in small bowel transplant recipients. METHODS: Five small bowel transplanted patients underwent capsule enteroscopy with the GIVEN endoscopy system. The results of capsule enteroscopy were compared with those of trans-stomal ileoscopy. RESULTS: Capsule enteroscopy was better tolerated than ileoscopy and good quality images of the small bowel were obtained in four patients. The terminal ileum was normal both on ileoscopy and capsule enteroscopy. Mucosal changes in segments not reached by ileoscopy were detected by capsule enteroscopy in three of four patients. CONCLUSIONS: Capsule enteroscopy is better tolerated than ileoscopy, allows complete exploration of the transplanted graft and can detect mucosal changes in segments not reached by ileoscopy.     

二氮嗪预处理对大鼠离体缺血/再灌注心肌保护作用的研究

目的 探讨二氮嗪预处理（DPC）对心肌缺血/再灌注损伤保护作用的机制。方法 Wistar大鼠26只,建立离体心脏Langendorff灌注模型,随机分成4组,即:①缺血/再灌注组（I/R组,n=10）:在心脏平衡灌流30 min后,缺血30 min再灌注K-H液1 h。②二氮嗪预处理组（DPC组,n=10）:在心脏平衡灌流10 min后,给予含二氮嗪（100μmol/L）的K-H液灌注5 min,再复灌不含二氮嗪的K-H液5 min后,给予含二氮嗪的K-H液灌注5 min;再复灌不含二氮嗪的K-H液5 min,然后缺血30 min,再灌注K-H液1 h。③空白对照组(n=3):用等量盐水代替二氮嗪,过程同DPC组。④二甲基亚砜组（DMSO组,n=3）:用DMSO代替二氮嗪,过程同DPC组。取4组大鼠心尖肌制作冰冻切片和电镜标本。前者用于免疫组化染色检测过氧化物酶体增生激活受体γ协同刺激因子1α（PGC-1α）的表达;后者用于对心肌线粒体进行Flameng评分。结果 I/R组、DPC组、空白对照组和DMSO组的PGC-1α平均积分吸光度值（IODA）,分别为（3.88±1.72）、（8.40±3.64）、（3.40±2.44）和（3.69±1.92）,DPC组与其他组比较PGC-1α的表达明显增高（P<0.05）。Flameng评分:I/R组为（1.78±0.14）,DPC组为（0.47±0.10）,空白对照组为（1.69±0.23）、DMSO组为（1.72±0.17）,DPC组较其他组线粒体的损伤明显减轻（P<0.01）。结论 DPC后,心肌中PGC-1α的表达明显增加,线粒体的损伤明显减轻,提示DPC对心肌的保护作用与PGC-1α的高表达有关,PGC-1α可能是一种内源性心肌保护物质。     

链激酶对大鼠肝脏缺血再灌注损伤的保护作用

目的:研究链激酶对大鼠肝脏缺血再灌注损伤的保护作用.方法:36只Wistar大鼠随机分成3组,每组12只.对照组大鼠肝脏经门脉10 mL乳酸林格液灌洗后,低温4℃UW液中保存24h.实验组大鼠肝脏经含链激酶7500 IU乳酸林格灌洗后,分别低温或低温静脉持续氧气灌注保存24 h后.离体常温再灌注45 min,观察灌洗液谷氨酰胺丙氨酸转氨酶(alanine aminotransferase.ALT)、谷氨酸乳酸脱氢酶(glutamate-lactate dehydrogenase,GLDH)和嘌呤核苷磷酸化酶(purine nucleoside phosphorylase,PNP)活性及肝脏胆汁分泌量、肝组织5'核苷酸酶活性的变化.结果:实验组再灌注过程中灌洗液ALT、GLDH和PNP活性均明显降低于对照组(P＜0.05或P＜0.01);胆汁分泌量增加[3.7±0.7μL/(g·45 min),9.1±0.μL/(g·45 min)vs1.1±0.9μL/(g·45 min),P＜0.05,P＜0.01);5'核苷酸酶活性染色明显增强.结论:链激酶改善低温保存肝脏的微循环,减轻缺血再灌注损伤.     

苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用

目的: 探讨苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用及机制.方法:采用大鼠30%小体积肝移植模型, ♂SD大鼠322只随机分为假手术组、小体积肝移植对照组和高、低剂量苦参碱治疗组(60、40 mg/kg). 观察术后1 wk生存率, 检测移植术2h、4 h、1 d、2 d、3d、7 d后ALT、AST及LDH值. 光镜及电镜下评估移植肝病理形态学改变, ELISA法检测肝脏IL-6, TNF-α表达.结果: 与对照组比较, 苦参碱高、低剂量治疗组术后1 wk生存率显著增加(80%, 70% vs 50%, 均P<0.05), 术后2h、4h、1d ALT、AST及LDH明显降低(P<0.01). 苦参碱治疗组中肝细胞和肝窦内皮细胞凋亡减少、细胞形态明显改善, 苦参碱治疗组术后2 h、4 h、1 d肝脏组织中IL-6, TNF-α水平明显降低(P<0.01). 结论:苦参碱可减轻肝细胞及肝窦内皮细胞的损伤, 改善小体积肝移植术后缺血再灌注损伤, 其机制可能与苦参碱抑制肝移植术后IL-6、TNF-α等炎症因子的释放有关.     

Liver,pancreas and small bowel transplantation: Current ethical issues

We describe the medical state of the art in liver, pancreas and small bowel transplantation, and portray the ethical issues. Although most ethical questions related to these transplantations are not specific for liver, pancreas and small bowel, they do challenge ethical analysis as well as new policies and clinical procedures. Firstly, outcomes continue to be of utmost concern, as information is only limited available, is developing over time and is surrounded by many uncertainties. Secondly, characteristics of donors and recipients should be carefully evaluated. The question of what qualifies a donor and a recipient should be considered against the background of a quest for extended criteria, embracing marginal cases, and a judgment with regard to what counts as a good enough outcome. Thirdly, ethical principles of autonomy and fairness are pushed, given the circumstance of severe scarcity, towards limits that can easily be crossed.     

Diagnosis and treatment of acute rejection in the first case of human living-related small bowel transplantation with a long-term survival in China

AIM: To report the comprehensive diagnosis and treatment of acute rejection in the first case of living-related small bowel transplantation with a long-term survival in China. METHODS: A 18-year-old boy with short gut syndrome underwent living-related small bowel transplantation, with the graft taken from his father (44-year old). A segment of 150-cm distal small bowel was resected from the donor. The ileo-colic artery and vein from the donor were anastomosed to the infrarenal aorta and vena cava of the recipient respectively. The intestinal continuity was restored with an end-to-end anastomosis between the recipient jejunum and donor ileum, and the distal end was fistulized. FK506, MMF and prednisone were initially used for post-transplant immunosuppression. Endoscopic observation and mucosal biopsies of the graft were carried out through the terminal ileum enterostomy; serum was collected to detect the levels of IL-2R, IL-4, IL-6 and IL-8. The change of the graft secretion and absorption was observed. RESULTS: Acute rejection was diagnosed promptly and cured. The patient was in good health, 5 years after livingrelated small bowel transplantation. CONCLUSION: The correct diagnosis and treatment of acute rejection are the key to the long-term survival after living-related small bowel transplantation.     

Fatal cytomegalovirus necrotising enteritis in a small bowel transplantation adult recipient with low pp65 antigenaemia levels

Although advances in immunosuppressive therapy have led to increased survival of solid organ transplantation recipients, it is well established that current protocols have been associated with an increased risk of developing tissue-invasive infections. In particular, cytomegalovirus still represents an important cause of morbidity. We report a case of cytomegalovirus infection involving the graft ileum with documented necrotising enteritis that developed after small bowel transplantation. The patient, a 56-year-old Caucasian female with a postsurgery short bowel syndrome, underwent a small bowel transplantation. Immunosuppression was maintained by combination of tacrolimus, steroids and daclizumab. Both the donor and the recipient were serologically negative for cytomegalovirus IgG. Nevertheless, ganciclovir prophylaxis was given for 21 days after surgery, as standard procedure. On hospital day 174, routine pp65 antigenaemia resulted positive (14/200,000 peripheral blood leukocytes). The patient was asymptomatic and preemptive ganciclovir therapy was instituted. In the following 3 days, due to a cytomegalovirus antigenaemia increase, ganciclovir was changed to foscarnet with subsequent virological response (7/200,000 peripheral blood leukocytes, on day 181). Two days later, the patient complained of acute abdominal pain and she underwent surgery for the diagnosis. Since the intraoperative findings consisted of a diffuse acute purulent peritonitis, the intestinal graft, together with native rectum, was removed. Biopsy specimens showed evidence of tissue-invasive cytomegalovirus infection. Postsurgery, the patient developed septic shock and died on day 198 as a consequence of multiple organ failure.     

左旋精氨酸对犬实验性冬眠心肌的保护作用

目的 :观察左旋精氨酸对冬眠心肌功能、代谢与结构的影响。方法 :30只犬短期冬眠心肌模型随机分为 3组 :A组 （n=14）灌注生理盐水 ;B组 （n=8）灌注左旋精氨酸 ;C组 （n=8）灌注 L- MNNA。结果 :3组间左心室舒张末期压、血乳酸、ATP含量及电镜下结构改变差异显著。左旋精氨酸组明显优于其他两组。结论 :左旋精氨酸可改善冬眠心肌、代谢与功能结构。     

Graft-versus-host disease after small bowel transplantation is associated with host colonic injury

The present studies were undertaken to evaluate the histologic effects of graft-versus-host disease on the host colon after small bowel transplantation. Graft-versus-host disease was produced in six Lewis × Brown Norway F₁ rats by performing vascularized, out-of-continuity small bowel transplants from parental Lewis donors. Host proximal and distal colon were sampled 14 days after operation when signs of graft-versus-host disease, including weight loss and spenomegaly, were present. Tissue was assessed histologically by blinded observer and compared to eight sham-operated controls. Three histologic features were noted to be statistically increased in diseased animals: (1) mucin loss; (2) crypt abscesses; and (3) large lymphoid aggregates in the mucosa and submucosa. These features were more commonly noted in the distal rather than the proximal, colon. Another group of five grafted animals treated with cyclosporine A (10 mg/kg/day intramuscularly) still lost weight but did not display overt signs of graft-versus-host disease and had normal-sized spleens. There was normal mucin content and no evidence of crypt abscesses in these treated animals, although large lymphoid aggregates were present. It is concluded that mucin loss, crypt abscesses, and large lymphoid aggregates are characteristics of graft-versus-host disease-induced colonic injury in this model and that these changes are most evident in the distal colon. Cyclosporine A therapy does not completely reverse the histological changes of colonic graft-versus-host disease. This model may be useful in studying the mechanisms by which immune mediated colitides preferentially affect the distal colon.