克服异种器官移植排斥反应的对策

进行异种器官移植需要解决种间免疫排斥反应(HAR，DXR和TMR)及猪的内源性逆转录病毒(PERV)的问题。基因工程及体细胞克隆猪的出现为克服异种器官移植中的障碍开辟了新的途径。本文对近年来的研究进展做一综述.。     

穿孔素在大鼠肝移植急性排斥的早期表达及意义

探索激活的细胞毒Ｔ细胞巴细胞的穿孔素途径,大鼠肝移急性排斥的早期表达及诊断价值。在建立大鼠肝移植急性排斥模型的基础上,应用免疫组化和逆转录聚合酶链反应检测移植肝穿孔素的素达,并以同在肝移植对照。     

宫内注射胎肝细胞对大鼠肝移植排斥反应的影响

目的：研究宫内注射胎肝细胞对大鼠移植免疫反应状态的影响。方法：将LOU／CN大鼠的胎肝细胞注射子宫内CHN胎鼠的腹腔。以分娩7－9wk龄时的CHN雄性大鼠作为受体，LOU／CN雄性大鼠作为供体，进行原位肝移植。观察受体大鼠存活时间，并以混合淋巴细胞培养检查移植排斥反应状态。结果：和对照组相比较，宫内注射组大鼠的存活时间明显延长。 混合淋巴细胞培养显示，移植排斥反应被明显抑制（P＜0．01）。结论：胎肝细胞宫内注射于胎鼠可延长大鼠肝移植的存活期，使移植排斥反应产生明显的抑制作用。     

DA→LEW大鼠肝脏急性排斥反应模型的技术改进与评价

目的:建立大鼠肝脏移植急性排斥反应模型并改进其手术技巧,对所建模型进行评价。方法:采用近交系雄性DA大鼠60只,Lewis大鼠120只,分为两组,其中A组30例:Lewis大鼠为供体(n=30),Lewis大鼠为受体;B组60例:DA大鼠为供体(n=60),Lewis大鼠为受体。采用改良“二袖套”法建立肝脏移植模型,观察手术成功率、平均存活时间、术后第1、3、5、7和10 d各时相点血清丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)水平以及移植肝脏的病理学变化。结果:手术成功率为93.3%(84/90);总耗时(90.0±15.0)min;无肝期时间(14.2±2.6)min;平均存活时间A组超过100d,B组(16.2±1.4)d;术后第5 d B组血清ALT和TBIL升高,与A组比较差异非常显著(P<0.01);B组移植肝脏病理检查有明显的排斥反应,而A组没有。结论:DA→LEW(Lewis)大鼠的品系组合是稳定的肝脏移植急性排斥反应模型;通过改进手术技巧提高了手术成功率,为进一步研究提供技术保障。     

T细胞疫苗联合环孢素A抑制大鼠肝移植排斥反应实验研究

目的：研究特异性T细胞疫苗接种联合环孢素A（CsA）对大鼠肝移植排斥反应的抑制作用。方法：利用LOU／CN大鼠的脾细胞免疫CHN大鼠，取后者脾细胞活化所制备的T细胞疫苗对肝移植受体的CHN大鼠进行免疫，移植时联合CsA，以大鼠肝移植后的存活时间、混合淋巴细胞培养、微量细胞毒测定对该方法抗大鼠肝移植排斥反应的作用加在证实。结果：和对照组相比较，T细胞疫苗接种联合CsA使肝移植大鼠存活期明显延长（P＜0.01），淋巴细胞转化率等排斥反应指标也具有显著性差异（P＜0.01）。结论：T细胞疫苗接种联合CsA能显著延长异品系大鼠肝移植的存活期，有明显的抗排斥反应作用。     

肾移植后急性排斥反应二例

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胰腺移植急性排斥反应的监测

探讨如何监测胰腺十二指肠移植急性排斥反应 ,用 12头猪作同种异体胰腺十二指肠移植 ,其中 6头术后抗排斥治疗 1周。定期取胰腺组织病理检查确定有无急性排斥反应 ,定期检测胰腺淀粉酶分泌量 ,血清TNF α和一氧化氮 (NO)变化。结果显示 ,一旦发生胰腺急性排斥反应 ,淀粉酶分泌急剧下降 ,TNF α及NO则明显升高 ,与急性排斥反应发生前比较有显著差异 (P <0 .0 1)。提示胰液淀粉酶分泌量、血清TNF α和NO均可用于监测胰腺急性排斥反应 ,指导适时进行胰腺活检早期诊断。     

肝脏移植术后体液性排斥反应的研究进展

体液性排斥反应即抗体介导的排斥反应(AMR),是造成移植物失功的重要因素.针对肾脏移植术后AMR的诊断与治疗,移植专家已经积累了一定经验,但肝脏移植术后AMR近年来才逐渐引起关注.肝脏与肾脏移植术后AMR既有相似也有不同之处,肝脏移植术后AMR包括超急性排斥反应(HAR)、急性排斥反应(AHR)、慢性排斥反应(CHR)及适应状态4种类型.本文对其发生机制及临床诊断要点(临床表现、常用血清学指标以及病理标准等)进行分析,对不同类型肝移植术后AMR的危险因素,以及不同类型肝移植术后AMR的预防和治疗进展进行阐述.     

移植肝排斥反应血管和胆管改变的MR表现

目的：探讨磁共振血管造影（MRA）和胰胆管成像（MRCP）对诊断肝移植术后排斥反应的价值。方法：6例原位肝移植术（OLT）后排斥反应患者均用磁共振（MR）快速自旋回波（TSE）序列及快速小角度激发梯度回波（FLASH）序列常规扫描、磁共振胆管成像（MRCP）、钆喷替酸葡甲胺（Gd-DTPA）动态增强3D MRA检查,分析各序列图像特点。结果：①形态和信号改变：6例患者均有肝脏体积增大,饱满。仅1例重度急性排斥反应患者肝实质信号异常;②血管异常表现：1例急性排斥反应肝左动脉串珠样改变及供体段门静脉明显变细。1例急性排斥反应肝静脉末梢分支杵状扩张而下腔静脉吻合口通畅。其余4例血管无明显异常表现;③胆管异常表现：4例急性排斥反应患者肝内胆管纤细稀疏,1例肝内胆管未显影,1例无明显异常表现。3例慢性排斥反应患者中2例肝内胆管分支稀疏并左肝管串珠样改变;1例胆总管胆泥形成而肝内胆管未见扩张。结论：肝移植术后排斥反应有一些特征性的血管和胆管MR表现。磁共振血管造影和胆管造影作为一种非侵袭性影像检查方法,可以辅助临床诊断肝移植术后排斥反应。     

单/多克隆抗体在肾移植急性排斥反应中的临床应用研究

目的：探讨应用抗淋巴细胞单克隆／多克隆抗体治疗肾移植术后急性排斥反应的效果、安全性和副反应等。方法：我中心施行同种异体肾移植术后对激素冲击治疗不敏感的急性排斥患者43例，分为两组，分别给予单克隆抗体OKT3和多克隆抗体ALG治疗，并对治疗效果、安全性和药物副反应等进行分析。结果：ALG治疗25例，排斥逆转16例，治愈率64％；OKT3组18例，排斥逆转15例，治愈率83．3％；两组有显著性差异（P〈0．05）。结论：单／多克隆抗体作为肾移植术后排斥反应的治疗用药，临床效果肯定．可使一部分患者避免因排斥反应丧失移植肾。但同时它们进入人体能引起首剂综合征等很多副反应，应当引起重视。OKT3治疗耐激素性急性排斥反应效果优于ALG。     

急性胰腺炎伴肝损害78例临床分析

目的探讨急性胰腺炎（AP）患者合并肝损害的发病机制、临床特点。方法对128例AP患者的临床资料进行回顾性分析。结果 128例AP中有78例合并肝损害,发生率为60.9%。其中重型急性胰腺炎（SAP）较轻症急性胰腺炎（MAP）肝损害发生率更高,损害程度更明显,差异均具有统计学意义（P〈0.05）。结论 AP大多伴有肝损害,其损害程度可反映急性胰腺炎严重程度,并与其病程有关。     

超声心动图评价大鼠异位移植心脏急性排斥反应的初步实验研究

目的:探讨高频超声心动图评价大鼠颈部异位移植心脏的急性排斥反应的价值。方法:采用高频超声心动图测量17只同种异体移植及6只同系移植心脏测量左室内径、心肌厚度、左室重量和心功能等。6只同系移植大鼠和9只同种异体移植大鼠,分别于移植术后第1、3、5天,采用高频超声对上述指标进行测量,第五天测量完毕后处死并做病理检查。另8只同种异体移植心脏,分别于移植术后第1、3天各测量一次,第3天测量完毕后处死做病理学检查,超声指标与病理结果相对照。结果:①同种异体移植术后,随着移植时间的延长,左室心肌厚度和左室重量逐渐增加,左室内径减小,射血分数无显著性改变;②术后第3天,组织学检查表明已有排斥反应发生,超声检查显示室壁厚度与左室重量明显增加,而常规心脏触诊未能及时发现排斥反应;③随着组织学分级加重显示的排斥,左室心肌厚度与左室重量有显著的增加。结论:室壁厚度和左室重量为超声评价排斥反应发生的敏感、准确指标。高频超声为心脏移植实验研究评价排斥反应提供了一种较为简便可靠的观察方法,为临床上心脏移植的排斥反应的超声评价提供了依据。     

Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2 (1/s) values in the cortex and medulla as well as the R2 ratio of the medulla to cortex (R2 ratio of M/C) were recorded. The R2 values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2 ratio of M/C. All the R2 values in the acute rejection group were lower than those in the normal function grafts group (P<0.001). Moreover, in the 9 patients as normal function, the R2 values of the cortex and medulla were different from the normal function grafts, which was lower in 5 patients and was higher in the 4 remaining patients. Conversely, the R2 ratios of M/C of the 9 patients were similar to those in the normal function group. BOLD MRI shows that decreased R2 values of the cortex and medulla and R2 ratio of M/C suggest acute renal graft rejection; furthermore, a steep R2 ratio of M/C (>1.1) is an important reason for keeping clinical normal function.     

分次灌注海水致兔呼吸窘迫综合征模型的建立

目的通过向兔气管插管内灌入海水，建立海水淹溺致急性呼吸窘迫综合征模型。方法14只新西兰大白兔被随机平分为C组（对照组，无任何处理）和S组（海水组，用海水灌注）。观察分次适量海水灌入气管插管后症状学、血气分析、血液动力学、血清中肿瘤坏死因子（TNF—α）和白细胞介素-6（IL-6）的变化。2h后给每组试验兔拍摄肺CT片，并观察其组织病理学变化。结果与C组相比，S组的O2和CO2指数显著降低（P〈0．01），呼吸动力学和血液动力学的情况明显恶化。TNF—α和IL-6增高，这一结果提示肺损伤发生于兔被海水灌注之后。另外，还发现模型兔有明显的肺水肿、肺泡隔断裂和炎性渗出。结论成功复制了既符合海水淹溺的实际情况，又符合国内外急性呼吸窘迫综合征诊断标准的海水淹溺致急性肺损伤动物模型。     

Towards non-invasive diagnostic techniques for early detection of acute renal transplant rejection: A review

The kidney is a very important complicated filtering organ of the body. When the kidney reaches stage 5 chronic kidney disease, end stage renal failure, the preeminent therapy is renal transplantation. Although it is the best form of treatment, lack of kidney donors is still challenging. Therefore, all efforts should be employed to prolong the survival rate of the transplanted kidney. However, graft dysfunction (e.g., acute rejection) is one of the serious barriers to long term kidney transplant survival. Currently, graft dysfunction’s gold standard of diagnosis is renal biopsy. Although renal biopsy is helpful, it is not preferred due to its invasive nature, high morbidity rates, and expensiveness. Therefore, noninvasive imaging techniques have become the subject of extensive research and interest, giving a strong promise to replace, or at least to decrease, biopsy usage in diagnosing graft dysfunction. This survey will discuss not only the current diagnosis and treatment of graft dysfunction but also the state-of-the-art imaging techniques in detecting acute renal transplant rejection.     

肝脏移植术后体液性排斥反应的诊断与治疗

目的寻找体液因素参与肝脏移植排斥反应的相关证据,探索临床监测和治疗体液性排斥反应的合理方案。方法通过检测肝脏移植术后肝穿组织中补体C4d、CD20(B细胞)和CD138(浆细胞)的表达情况,诊断肝损伤患者是否存在体液性排斥反应。临床结合病理诊断为排斥反应时,首先增加他克莫司(普乐可复)用量,肝功能损害严重者采用激素冲击治疗;诊断为体液性排斥反应的患者激素冲击治疗无效后,给予抗胸腺细胞球蛋白(ATG)或雷帕霉素(RPM)治疗。结果16例患者共进行25次肝脏穿刺检查,病理检查结合临床表现,10例患者诊断为体液性排斥反应15次,4例患者诊断为细胞性排斥反应6次,另外2例患者均先后诊断为急性和慢性排斥反应。体液性排斥反应激素冲击治疗有效率(29.4%,5/17)明显低于细胞性排斥反应(87.5%,7/8)。7例患者12次肝损害时诊断为耐激素性体液性排斥反应,在激素冲击治疗无效后1例给予ATG治疗,5例加用RPM,排斥反应均得以纠正,另外1例接受"O"型供肝的"AB"型患者出现2次肝功能明显异常,采取多种治疗方法无效,最终因肝功能衰竭死亡。结论体液免疫因素可能参与了部分肝脏移植急、慢性排斥反应的发生。应用ATG和RPM治疗体液性排斥反应较为有效。     

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model

¹¹¹In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin. Offprint requests to: U. Scheffel, Sc.D.     

19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells

Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron‐oxide labeled immune‐cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T‐weighted images. In this study, we tested the feasibility of using a fluorine‐based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine‐19 (¹⁹F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro‐15‐crown‐5‐ether, we observed ¹⁹F‐signal intensity in the organs experiencing rejection by ¹⁹F MRI, and conventional ¹H MRI was used for anatomical context. Immunofluorescense and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, ¹⁹F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.