国际首例6-基因编辑猪-猴肝肾联合移植围术期治疗研究
Perioperative treatment of the first international 6-gene-edited pig-to-rhesus macaque combined liver and kidney transplantation
韩士超 1马帅军 1戚若晨 1王国辉 1张小燕 1刘克普 1范效铮 1魏迪 1张玄 2杨晓剑 1陶开山 2秦卫军 1窦科峰2
作者信息
- 1. 空军军医大学西京医院泌尿外科,陕西西安 710032
- 2. 空军军医大学西京医院肝胆外科,陕西西安 710032
- 折叠
摘要
目的 探讨国际首例6-基因编辑猪-猴肝肾联合移植模型的构建,探究异种肝脏移植对异种肾脏移植的影响.方法 将人源化6-基因编辑猪的肝脏、肾脏移植给恒河猴受体,肝脏移植采用腹腔异位移植,肾脏移植采用原位移植,保留对侧肾脏,观察血流灌注恢复后,移植肝、肾的情况及受体存活情况;定期进行移植物超声及功能检查;监测受体猴生化指标及生理指标变化;受体猴生命终点取移植肾、移植肝进行病理检查.结果 手术历时14 h结束,术后受体猴各项生理指标基本正常,移植物开放血流后可见移植肝灌注良好,即刻可见胆汁流出;移植肾灌注良好,即刻可见尿液流出,未见明显超急性排斥反应发生;术后移植肾功能良好,术后5d移植肾尿量减少,考虑排斥反应发生,术后受体猴最终存活14 d.结论 多基因编辑猪-猴异种肝肾联合移植模型构建成功,术后移植肾未见明显超急性排斥反应发生,异种肝移植可减轻异种肾脏移植急性排斥反应发生.
Abstract
Objective To investigate the establishment of the first international 6-gene-edited pig-to-rhesus macaque combined liver and kidney transplantation model,and to explore the influence of liver xenograft on kidney xenograft.Methods The liver and kidney of humanized 6-gene-edited pig were transplanted to rhesus recipient.Heterotopic abdominal transplantation was used for liver transplantation and orthotopic transplantation for kidney transplantation,with the contralateral kidney retained.The condition of the transplanted liver and kidney and the recipient survival were observed after blood perfusion recovery.Regular graft ultrasound was performed to examine the function of grafts.The changes of biochemical and physiological indexes were monitored.At the end of life of the recipient,the transplanted kidney and liver were taken for pathological examination.Results The operation lasted for 14 h and the physiological indexes of the recipient were basically normal after operation.After the open blood flow of the grafts,the transplanted liver was well perfused and bile outflow was immediately visible.The perfusion of the transplanted kidney was good,urine outflow could be seen immediately,and no obvious hyperacute rejection was observed.After operation,the transplanted kidney function was good,and the urine volume of the transplanted kidney decreased 5 d after operation attributing to rejection reaction.The recipient survived for 14 d after operation.Conclusion The multi-gene-edited pig-to-rhesus macaque combined liver and kidney transplantation model was successfully constructed,and no obvious hyperacute rejection was observed in the transplanted kidney after operation.Xenograft liver transplantation may alleviate the acute rejection of xenograft kidney transplantation.
关键词
异种移植/基因编辑猪/肝肾联合移植/排斥反应Key words
xenotransplantation/gene-edited pigs/combined liver and kidney transplantation/rejection reaction引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据