基因编辑猪-猴异种组织器官移植围手术期动物护理

doi:10.12300/j.issn.1674-5817.2024.043

实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (5): 495-501.DOI: 10.12300/j.issn.1674-5817.2024.043

基因编辑猪-猴异种组织器官移植围手术期动物护理

朱婵¹(), 张栋梁¹, 赵德莉¹, 石雪琴¹, 千磊², 张玄³, 金艳⁴, 段伟⁵, 戚若晨⁶, 刘超华⁷, 杨薛康¹, 韩军涛¹(), 潘登科⁸()

^1.空军军医大学第一附属医院全军烧伤中心/烧伤与皮肤外科, 西安 710032
^2.空军军医大学实验动物中心, 西安 710032
^3.空军军医大学第一附属医院肝胆外科, 西安 710032
^4.空军军医大学第一附属医院心脏外科, 西安 710032
^5.空军军医大学第一附属医院骨科, 西安 710032
^6.空军军医大学第一附属医院泌尿外科, 西安 710032
^7.空军军医大学第一附属医院整形外科, 西安 710032
^8.成都中科奥格生物科技有限公司，成都 610095

收稿日期:2024-03-12 修回日期:2024-08-06 出版日期:2024-11-06 发布日期:2024-10-25
通讯作者: 韩军涛（1968—），男，博士，主任医师，教授，硕士研究生导师，研究方向：各种烧烫伤的综合救治。E-mail： hanjt@fmmu.edu.cn；
潘登科（1972—），博士，研究员，研究方向：异种器官移植。E-mail: pandengke2002@163.com
作者简介:朱婵（1985—），女，本科，主管技师，研究方向：烧伤康复。E-mail： xuanxuan85@163.com
基金资助:
陕西省重点研发计划“TIGIT-Fc重组蛋白诱导异种移植免疫耐受的机制及应用”(2021SF-107);空军军医大学第一附属医院2024年度医务人员培养助推立项资助计划“多基因编辑猪皮用于深度烧伤创面的安全性和有效性研究”(XJZT24LZ06)

Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys

ZHU Chan¹(), ZHANG Dongliang¹, ZHAO Deli¹, SHI Xueqin¹, QIAN Lei², ZHANG Xuan³, JIN Yan⁴, DUAN Wei⁵, QI Ruocheng⁶, LIU Chaohua⁷, YANG Xuekang¹, HAN Juntao¹(), PAN Dengke⁸()

^1.Department of Burns and Cutaneous Surgery, Burn Center of PLA, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^2.Laboratory Animal Centre, Air Force Medical University, Xi'an 710032, China
^3.Department of Hepatobiliary Surgery, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^4.Department of Cardiac Surgery, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^5.Department of Orthopedics, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^6.Department of Urinary Surgery, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^7.Department of Plastic Surgery, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
^8.Chengdu Clonorgan Biotechnology Co. , Ltd. , Chengdu 610095, China

Received:2024-03-12 Revised:2024-08-06 Published:2024-10-25 Online:2024-11-06
Contact: HAN Juntao, E-mail: hanjt@fmmu.edu.cn;
About author:First author contact:PAN Dengke, E-mail:pandengke2002@163.com

摘要/Abstract

摘要：

目的探讨基因编辑猪-猴异种组织器官移植围手术期的动物护理，为提高猪-猴异种组织器官移植实验的成功率提供帮助。方法 2022年10月—2023年10月，对行基因编辑猪-猴异种组织器官移植的7只受体恒河猴进行围手术期护理和伤口保护。根据体型及手术区域，为受体猴定制伤口防护服以保护伤口，同时做好围手术期精细化护理。其中，术前护理包括术前准备、术前用药等；术中护理包括生理指标监护和麻醉手术护理等；术后护理包括伤口保护、观察监测、营养护理等。结果 7只恒河猴的异种组织器官移植手术均获得成功。通过伤口防护服的保护和精细化护理，所有恒河猴手术伤口均一期愈合，术后恢复良好。结论做好猪-猴异种组织器官移植围手术期的护理和伤口保护，不仅能促进伤口愈合，还能减轻手术给动物带来的疼痛和伤害，这对猪-猴异种组织器官移植的实验研究进展和提升动物福利均具有重要意义。

关键词: 基因编辑猪, 异种器官移植, 恒河猴, 护理, 伤口保护装置, 实验动物福利

Abstract:

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Key words: Genetically edited pig, Xenotransplantation, Rhesus monkey, Care, Wound protection device, Laboratory animal welfare

中图分类号:

R-332

朱婵,张栋梁,赵德莉,等. 基因编辑猪-猴异种组织器官移植围手术期动物护理[J]. 实验动物与比较医学, 2024, 44(5): 495-501. DOI: 10.12300/j.issn.1674-5817.2024.043.

ZHU Chan,ZHANG Dongliang,ZHAO Deli,et al. Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys[J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 495-501. DOI: 10.12300/j.issn.1674-5817.2024.043.

图/表 4

图1 异种组织器官移植围手术期的恒河猴伤口防护服制作过程注：A为身体测量数据（左为正面，右为背面，数据单位为cm）；B为伤口防护服的设计图；C为成品（这是不包括四肢的基础款；左为正面，右为背面，有多条拉链，用于调整松紧度）；D为行异种膝关节移植术后恒河猴穿戴伤口防护服（这是包含裤子的款型；左为术后即刻，右为术后一周）。

Figure 1 Manufacturing process of wound-protective garments for rhesus monkeys during perioperative period of xenotransplantationNote：A, Body measurements of a monkey (the left shows the front of the monkey, the right shows the back of it, unit: cm.) B, Design drawing of the wound-protective clothing. C, Finished suit (this is a basic sample without limb coverage; the left shows the front of the garment, the right with zippers shows the black of it). D, Rhesus monkeys wearing wound-protective clothing after xenograft knee joint transplantation (sample with pants; the left shows the monkey just after surgery, the right shows the monkey a week after surgery).

表1 异种组织器官移植手术的受体恒河猴资料

Table 1 Information of recipient rhesus monkeys undergoing xenotransplantation surgery

编号 Number	性别 Sex	年龄/year Age/year	体重/kg Weight/kg	移植组织或器官Transplanted tissue or organ	手术时长/h Operating time/h	并发症 Complication	存活时间/d Survival time/d	伤口愈合Wound healing
1	雄	8	11.0	肝脏	7.5	无	14	Ⅰ期愈合
2	雄	9	11.2	心脏	4.0	无	20	Ⅰ期愈合
3	雄	10	10.0	肾脏	4.5	无	27	Ⅰ期愈合
4	雄	10	11.4	膝关节	4.0	无	>365	Ⅰ期愈合
5	雄	11	10.6	角膜和皮肤	6.5	无	>365	Ⅰ期愈合
6	雄	12	12.0	颅骨和神经	6.0	无	>365	Ⅰ期愈合
7	雄	15	17.5	全层腹壁组织	8.0	无	13	Ⅰ期愈合

图2 行异种肾移植术后的恒河猴伤口愈合情况（腹部伤口）注：左为术后即刻；右为术后10 d拆线时。

Figure 2 Wound healing of rhesus monkeys after xenogeneic kidney transplantation (abdominal wound)Note：Left, immediately after surgery; Right, 10 days after surgery at the time of removing stitches.

图3 行异种皮片移植术后的恒河猴皮片成活情况注：从左到右依次为术后即刻、术后5 d、术后10 d、术后15 d和术后19 d。

Figure 3 Survival of skin grafts in rhesus monkeys after xenogeneic skin graft transplantationNote：From left to right， they are immediately after surgery， 5 days after surgery， 10 days after surgery， 15 days after surgery and 19 days after surgery.

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基因编辑猪-猴异种组织器官移植围手术期动物护理

Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys

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