无创影像学技术检测同种异体急性心脏移植排斥反应的研究

发布时间：2018-06-24 15:52

本文选题：带负荷 + 腹腔异位心脏移植　；参考：《首都医科大学》2015年博士论文

【摘要】：【目的】建立新型带负荷腹腔异位心脏移植兔模型，制定标准化操作流程，降低并发症发生率及死亡率，通过超声心动图比较传统模型及新模型的血流动力学特点。【方法】 30只3.5-4.0kg雄性同种异体新西兰大白兔，分为供体组及受体组，分别建立无负荷及带负荷腹腔异位心脏移植模型，无负荷（NW）组模型采用经典的Abbott方法，带负荷（VL）组模型采用改良的方法，首先行供心切取，麻醉后气管切开插管，正中开胸显露上下腔静脉和主动脉弓上血管，肝素化后经无名动脉插入灌注针头，心脏灌注停跳液后切取心脏，切取部分左右心房壁后将切口吻合，结扎肺动脉、下腔静脉和左右肺静脉，修剪好的心脏置于冰水中，麻醉受体，正中开腹显露肾下腹主动脉和下腔静脉，肝素化后将供心的上腔静脉和升主动脉分别与受体的下腔静脉和腹主动脉吻合，止血后关闭腹部切口。每日记录心搏强度积分、供心存活时间、血栓发生率、受体存活率及并发症发生率，超声记录每日供心及受体原位心脏血流动力学相关参数。【结果】 NW组出现1例麻醉意外死亡，VL组出现1例消化道症状，无肺部、脊髓并发症，多数供心在移植后7天停跳，NW组均可在左心内发现血栓形成，VL组左右心腔内未发现血栓形成；移植后5天内，VL组供心在每次收缩期主动脉瓣均可打开，而NW组供心主动脉瓣在整个心动周期中均维持关闭状态，供心最大主动脉瓣流速和舒张晚期二尖瓣流速约为原位心脏最大流速值的一半，，心房间分流以右向左为主，上腔静脉吻合口处为双向血流。【结论】本实验首次提出新型的兔腹腔异位心脏移植负荷模型，模型较理想的模拟了原位模型的血流动力学状态；建立的一系列技术改进和标准化操作流程提高了模型建立的成功率，但该模型仍无法完全模拟原位心脏的血流动力学状态。【目的】运用标记了核素18F的特异性示踪剂突触结合蛋白I（Synaptotagmin I），通过PET-CT技术显影，检测兔腹腔异位心脏移植急性排斥反应。【方法】 24只同种异基因新西兰大白兔分为移植后3天组（Group3）、移植后5天组（Group5）和移植后7天组（Group7），按照第一部分提供的方法建立带负荷的腹腔异位心脏移植模型，在移植后第3、5、7天，三组受体分别行PET-CT检查，经耳缘静脉注射18F-Synaptotagmin I，记录原位心脏及异位心脏的标准摄取值（SUV），影像数据采集后处死动物并取出原位心脏及供心，切取心脏不同部位组织进行HE染色、TUNEL免疫组织化学染色【结果】原位心脏、Group3、Group5和Group7供心的PET-CT标准摄取值（SUV）分别为0.91±0.04、0.94±0.05、1.09±0.09、2.40±0.38，原位心脏、Group3和Group5之间的SUV值无统计学差异，而原位心脏、Group3、Group5和Group7间的SUV值存在显著性差异，Group7的SUV值高于Group5。HE染色下原位心脏排斥级别为0级，Group3排斥级别以1A级为主，Group5排斥级别以2级为主，Group7排斥级别以4级为主；TUNEL结果显示原位心脏与Group3的移植心脏凋亡率间无统计学差异，但明显低于Group5及Group7组，Group3的移植心脏凋亡率低于Group5，明显低于Group7，而Group5与Group7的凋亡率无明显差异。【结论】 PET-CT可提供清晰的不同心脏部位的影像信号，非特异性摄取较少；移植心凋亡率随着移植时间延长而增加，高级别的排斥反应以大量心肌细胞死亡、大量炎症细胞浸润合并炎症细胞凋亡为主，存在排斥级别越高，整体凋亡率越高以及SUV值越高的趋势，SUV值与凋亡率的相关系数为0.542。在PET-CT下通过特异性分子示踪剂检测同种异体心脏移植排斥反应的实验研究显示出了该方法具有一定优越性，但要将该方法应用于临床还需更进一步的系统性基础和临床研究。
[Abstract]:Purpose of the project

To establish a new rabbit model with load abdominal ectopic heart transplantation , establish standardized operation flow , reduce the morbidity and mortality of complications , compare the traditional model with echocardiography and the hemodynamic characteristics of the new model .

Methodology

Thirty - three ( 3.5 - 4.0kg ) male allogeneic New Zealand rabbits were divided into two groups : donor group and receptor group , and no load and load - loaded abdominal ectopic heart transplantation model was established .

The result is not valid .

In the NW group , 1 case of anesthesia died unexpectedly , 1 case of digestive tract symptom occurred in VL group , no lung injury or spinal cord complication , most of donor heart was stopped 7 days after transplantation , NW group could find thrombus in the left heart , and no thrombosis was found in the left and right heart chambers of VL group ;
Within 5 days after transplantation , the center of the VL group could be opened in each systolic aortic valve , while the aortic valve of the NW group remained closed during the whole cardiac cycle . The maximum aortic valve flow rate and the late diastolic mitral valve flow rate were about half of the maximum flow velocity of the in - situ heart .

Conclusion

A new model of rabbit abdominal ectopic heart transplantation was proposed for the first time , and the model was ideal to simulate the hemodynamic status of the in situ model .
A series of technical improvements and standardized operational processes have been established to improve the success rate of the model establishment , but the model is still unable to fully simulate the hemodynamic state of the in - situ heart .

Purpose of the project

Synaptotagmin I ( Synaptotagmin I ) was used to detect the acute rejection of rabbit abdominal ectopic heart transplantation by PET - CT technique .

Methodology

Twenty - four allogenetic New Zealand rabbits were divided into three groups ( Group3 ) , 5 - day post - transplantation ( Group5 ) and 7 - day post - transplantation ( Group7 ) .

The result is not valid .

The SUV values of the in situ heart , Group3 , Group5 and Group7 were 0.91 卤 0.04 , 0.94 卤 0.05 , 1.09 卤 0.09 , 2.40 卤 0.38 , and the SUV values between Group3 and Group5 were significantly different . In - situ heart , Group3 , Group5 , and Group7 SUV values were significantly different .
TUNEL results showed that there was no significant difference in apoptosis rate between in situ heart and group 3 , but significantly lower than that of Group5 and Group7 . The apoptosis rate of transplanted heart in Group3 was lower than that of Group5 , which was significantly lower than that of Group7 , and no significant difference was found between Group5 and Group7 .

Conclusion

PET - CT can provide clear image signals at different cardiac sites , less specific uptake ;
The apoptosis rate of the transplanted heart increased with the time of transplantation , and the high - grade rejection was mainly caused by the death of a large number of myocardial cells . The higher the rejection level , the higher the overall apoptosis rate and the higher the SUV value , the higher the SUV value and the apoptosis rate , the higher the SUV value and the apoptosis rate showed that the method has certain advantages , but the method can be applied to the clinical research on the further systematic basis and clinical study .
【学位授予单位】：首都医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R654.2

【共引文献】