颈部袖套法建立小鼠-大鼠异种心脏移植模型

Establishment of a mouse-rat cervical cardiac xenotransplantation model by cuff technique

背景:小动物心脏移植模型是器官移植基础与临床研究的常用模型和重要手段,移植部位多为颈部和腹部。其中颈部异位移植最大的优点在于移植心位于颈部皮下,有利于对供心搏动情况进行直接观察,进而早期预判排斥反应的发生。目的:对小鼠-大鼠颈部异种心脏移植模型的麻醉方式、手术操作、围手术期处理等方面进行改进,以期建立更加稳定的动物模型。方法:采用改良袖套法建立异位异种心脏移植模型,将小鼠供心移植到受体大鼠的右侧颈部,主要改进了摘取供心的方法,并使用小动物麻醉机进行异氟烷吸入性麻醉。模型建立分为练习、稳定和定型3个阶段。取部分实验标本做组织病理学检查。结果与结论:模型建立练习阶段、稳定阶段和定型阶段手术成功率分别为53.33%,85.71%和96.15%,稳定及定型阶段手术成功率明显高于练习阶段(P<0.05);稳定和定型阶段手术总操作时间明显短于练习阶段(P<0.05)。组织病理学结果显示,异种心脏移植后出现供心血管内皮损伤、血栓形成、心肌实质损伤、间质出血和炎症细胞浸润等现象,较正常心脏和同系移植均有明显改变,并且有随移植术后时间延长而逐渐加重的趋势,证实了模型的可靠性。提示小鼠-大鼠颈部异种心脏移植模型操作简便、稳定可靠,短时间内即可熟练掌握,成功率高,是研究异种移植排斥反应的理想动物模型。

BACKGROUND： Small animal heart transplantation model is a common model and an important mean for basic and clinical research of organ transplantation, and the transplant part is often the neck and abdomen. The biggest advantage of cervical heterotopic transplantation is that the transplanted heart will located in the neck subcutaneous, which is conducive to the direct observation of the beating of donor heart, thus early anticipating the rejection. OBJECTIVE： To improve the anesthesia, surgical procedures and perioperative management of the mouse-rat cervical cardiac xenotransplantation model, in order to establish a more stable animal model. METHODS： The mouse-rat heterotopic cardiac xenotransplantation models were established by modified cuff technique to transfer the donor heart of mouse to the right side of the neck of rat, the method to remove the donor heart was improved, and the models received inhalation anesthesia of isoflurane with small animal anesthesia machine. The experimental levels of establishing the models were divided into practicing, stable and skilled stages. Part samples were taken for the histopathological examination. RESULTS AND CONCLUSION： In the three stages （practicing, stable, skilled） of establishing the models, the successful rates of surgery were 53.33%, 85.71%, and 96.15% respectively. The successful rate in stable and skilled stages was higher than that in the practicing stage （P 0.05）. The total operation time in the stable and skilled stages was significantly shorter than that in the practicing stage （P 0.05）. Histopathological examination results showed that the cardiovascular endothelial injury, thrombosis, myocardial parenchymal damage, interstitial hemorrhage and inflammatory cell infiltration after heterotopic cardiac xenotransplantation were more serious compared with normal heart transplantation and cardiac allograft, and showed a time-depend manner, which identify the reliability of the model. It suggests that the mouse-rat cervical cardiac xenotransplantation model is simple, reliable, easily operated in a short-time and has a high successful rate. It is an ideal animal model for studying xenotransplantation rejection.