犬活体肝移植模型的建立及评价*☆
张清军,潘明新,孔凡东,姚坤厚,高 毅
课题背景:建立器官移植的大动物模型是开展器官移植工作的前提和进行基础研究工作的平台。犬活体肝移植接近于临床实际,能模拟临床活体肝移植的全部过程。
应用要点:由于犬对内脏瘀血的耐受能力较差,无肝期需采用体外静脉转流或门体静脉分流。文章在受体手术时,将受体肝脏分两步切除,消除了无肝期,避免了体外转流和分流的应用,并用套管法来重建胆道,简便了手术步骤, 明显缩短了手术时间, 基本消除了长时间麻醉、手术及体外静脉转流等非必需因素对受体全身生理指标的影响, 具有更高的稳定性和存活率。
同行评价:活体肝移植动物模型的建立是目前国内外比较棘手的问题,主要原因是动物对无肝期的耐受力差。文章通过保留部分肝组织,而不进行静脉转流或分流,待门静脉开放后再切除剩余肝组织,虽然在临床上无法实现,但在动物模型的建立方面有很大的优越性,值得借鉴。
摘要
目的: 犬活体肝移植接近于临床实际,能模拟临床活体肝移植的全部过程。应用非体外转流和分流方法建立犬活体肝脏移植模型,以期为开展临床活体肝移植提供实验数据。
方法:①实验材料:实验于2006-05/2007-04在南方医科大学南方医院动物研究所完成,选用健康本地杂种犬36只,动物实验方法符合动物伦理学要求。②实验方法:将36只犬按随机数字表法分为供体组和受体组,共行非转流条件下犬活体肝脏移植手术18对次。活体供肝组行标准Ⅰ,Ⅱ,Ⅲ叶左半肝切取术。受体组先行左侧Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ叶肝脏组织切除,在新肝植入后,再切除原肝残留Ⅵ,Ⅶ叶肝组织。③实验评估:检测动物手术时间、术中失血量、输血量及存活期;犬死后当天行尸体解剖明确死亡原因。
结果:成功建立非转流犬活体肝移植模型14只。①活体供肝组手术结果:供体术中死亡1只,术后第1天因出血死亡1只,术后5 d存活率为88.2%。手术时间(183.7±32.4)min,失血量为(78.5±12.8)mL,输血量0 mL,供肝的热缺血时间几乎为零,冷缺血时间(146.7±24.4)min。②受体组手术结果:术中死亡4只,其中创面出血2只,左肝静脉吻合口出血1只,1只死于急性肺水肿。术后存活14只,术后5 h存活率为85.7%;受体犬手术时间(276.7±34.1)min,无肝期0 min;失血量为(242.5±25.6)mL,输血量(230.6±47.3)mL。
结论:犬是理想的活体肝移植动物模型,受体肝脏分两步切除,新肝植入期,可有效维持受体血循环稳定,免除了体外转流或门腔分流的操作,为临床开展活体肝移植提供了技术和经验的参考。
关键词:肝移植;疾病模型,动物;器官移植
张清军,潘明新,孔凡东,姚坤厚,高毅.犬活体肝移植模型的建立及评价[J].中国组织工程研究与临床康复,2008,12(5):809-812
[www.zglckf.com/zglckf/ejournal/upfiles/08-5/5k-809(ps).pdf]
南方医科大学珠江医院肝胆外科,广东省广州市 510282
张清军☆,男,1972年生,山东省费县人,汉族,南方医科大学在读博士,医师,主要从事肝移植基础与临床研究。
zhang72128@
163.com
通讯作者:高 毅,博士,教授,博士生导师,南方医科大学珠江医院肝胆外科,广东省广州市 510282 gaoyi6146@163.
com
广东省自然基金资助项目(C03020504)*
中图分类号: R657.3
文献标识码: A
文章编号: 1673-8225
(2008)05-00809-04
收稿日期:2007-07-09
修回日期:2007-09-27
(07-50-7-3749/G·Q)
Establishment and evaluation of living donor liver transplantation models in dogs
Abstract
AIM:Dog living donor liver transplantation superficially resembles the clinical experiment, and can simulate the whole process of clinical living donor liver transplantation. This article establishes an animal model of living partial liver transplantation without veno-venous bypass in dogs.
METHODS: ①Experiments were conducted in the Animal Institute of Nanfang Hospital Affiliated to Southern Medical University between May 2006 and April 2007. Thirty-six healthy hybrid dogs were selected. Animal intervention met the animal ethical standard. ②These dogs were randomized into 2 groups (18 as donors and 18 as recipients). Eighteen times living donor liver transplantation was performed under non-bypass flow condition. Standard Ⅰ,Ⅱ,Ⅲ left hepatic lobectomy was performed in living donor group. For recipient group, the recipient dogs underwent two steps total hepatectomy: Firstly, the segments Ⅰ,Ⅱ,Ⅲ,Ⅳand Ⅴ were resected. After the donor liver graft was then transplanted in an orthotopic position, the segments Ⅵ and Ⅶ were resected. ③Operation time, blood loss amount, blood transfusion amount and survival phase were determined. Dead dogs received autopsy to define the cause of death.
RESULTS: Fourteen dog models after non-bypass living donor liver transplantation were successfully established. ①Operation results of living donor group: One dog died during the operation, one dog died of bleeding on the first day after operation. The survival rate was 88.2% 5 days after the surgery. The mean operative time, amount of blood loss and amount of blood transfusion during the operation were (183.7±32.4) min, (78.5±12.8) mL, 0 mL, respectively. Warm ischemia time was zero and the average of cold ischemia time was (146.7±24.4) min. ②Recipient group: Four out of 18 dogs died intraoperatively including 2 surface wound bleeding, 1 left hepatic veins stoma bleeding and 1 acute pulmonary edema. The survival rate was 85.7% 5 hours after the surgery. The mean operative time, anhepatic phase, amount of blood loss and amount of blood transfusion during the operation were (276.7±34.1) min, 0 min, (242.5±25.6) mL, (230.6±47.3) mL, respectively.
CONCLUSION: Dogs are appropriate animal model for living donor liver transplantation. Technique of two steps total hepatectomy in the recipient is feasible and may effectively sustain the systematic circulation of recipient. This model provides opportunity to develop techniques for living donor liver transplantation in clinic.
Zhang QJ, Pan MX, Kong FD, Yao KH, Gao Y.Establishment and evaluation of living donor liver transplantation models in dogs.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(5):809-812(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-5/5k-809(ps).pdf]
Department of Hepatobiliary Sur-gery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
Zhang Qing-jun☆, Studying for doctor-ate, Physician, Department of Hepatobiliary Sur-gery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
zhang72128@
163.com
Correspondence to: Gao Yi, Doctor, Professor, Tutor of doctor, Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
gaoyi6146@163.com
Supported by: the Natural Science Foundation of Guangdong Province, No. C03020504*
Received:2007-07-09
Accepted:2007-09-27
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