非转流小型猪原位肝移植模型的建立及评价

Establishment and evaluation of orthotopic liver transplantation models without veno-venous bypass in miniature pigs

目的:建立标准化程度高、重复性和稳定性好的小型猪原位肝移植模型。方法:实验于2004-06/2006-02在南方医科大学南方医院动物研究所完成。选用健康中国版纳小型猪36只,按随机数字表法分为供、受体各18只,施行非转流小型猪原位肝移植手术18例。在非体外静脉转流的条件下行同种异体原位肝移植术,严格控制动物无肝期时间,应用套管法吻合胆总管,另外加强围手术期的处理,使无肝期的血压维持在满意水平。监测动物无肝期时间、手术时间、失血量、输血量及动物存活期;术中监测动物的血液动力学及动脉血气分析、生化指标变化;猪死后当天行尸体解剖明确死亡原因。结果:成功建立非转流小型猪原位肝移植模型18只,均纳入结果分析,无脱失。①实验动物无术中死亡,术后当天死亡1只,死亡原因为急性肺水肿;术后第2天死亡1只,死亡原因为胆总管吻合口胆瘘。术后7d存活率为88.9%。②手术时间、无肝期时间、术中失血量及输血量分别为(179.61±14.27)min,(27.28±3.43)min,(422.22±66.91)mL及(444.44±51.13)mL。③与无肝前期相比,实验动物无肝期平均动脉压、中心静脉压、pH值及碱剩余明显下降(P<0.05￣0.01),心率及血清钾水平显著升高(P<0.01);手术结束时平均动脉压及中心静脉压恢复,经药物调整后血清钾水平下降,pH值逐渐恢复。结论:非转流条件下的小型猪原位肝移植模型是肝移植实验的理想动物模型。

AIM： To establish animal model of orthotopic liver transplantation （OLT） in miniature pigs with high standardization, reproducibility and stability. METHODS： The experiment was conducted in the Animal Institute of Nanfang Hospital Affiliated to Southern Medical University between June 2004 and February 2006. Thirty-six miniature pigs were selected and randomly divided into receptors and donators with 18 pigs in each to perform OLT without veno-venous bypass in Homogeneity variant OLT was conducted without veno-venous by pass, and status in anhepatic phase was strictly controlled. Cannulation was adopted to inosculate the hepatocystic duct, and the management during peri-operation period was enhanced so as to maintain the blood pressure in a satisfactory level during the anhepatic phase. The time of anthepatic phase, operation time, amount of blood loss, amount of blood transfusion and the survival phase of animals were monitored. Hemodynamics and arterial blood gas analyses, changes in biochemical indicators were monitored during the OPeration. And animals were dissected after death to identify the cause of death. RESULTS： 18 miniature pigs were successfully made into models of OLT, and were involved in the analysis of results. No animals withdrew from the study. ① No animals died during the operation, while one pig died on the first day post-operation for acute pulmonary edema, and one pig died on the second post-operation for the biliary fistula in the stoma of hepatocystic duct. The suvival rate at 7 days after the surgery was 88.9%. ② The mean operative time, anhepatic phase, amount of blood loss and amount of blood transfusion during the oPeration were （179.6±14.27） minutes, （27.28±3.43） minutes, （422.22±66.91） mL and （444.44±51.13） mL resPectively. ③ During the anhepatic phase, the mean arterial pressure （MAP）, central venous pressure （CVP）, pH value and buffuer excess decreased dramatically （P 〈 0.05-0.01）, while the heart rate and serum potassium remarkably increased （P 〈 0.01）. After the surgery, .the MAP and CVP recovered, and the serum potassium decreased after regulation by drugs, and the pH value gradually recovered. CONCLUSION： The animal model of OLT without veno-venous bypass in miniature pigs is an ideal one for series studies related to liver transplantation.