巴马小型猪肝移植无肝期动物模型的建立  

Establishment of an animal model of Bama small pig liver transplantation with anhepatic stage

作　　者：范顺利 史源[2] 涂金鹏[1] 王凯[4] 霍志昊 孔德俊 王政禄[4] 郑虹[4] 吴迪[1] Fan Shunli;Shi Yuan;Tu Jinpeng;Wang Kai;Huo Zhihao;Kong Dejun;Wang Zhenglu;Zheng Hong;Wu Di(Department of Transplant Oncology,Tianjin First Central Hospital,Tianjin 300192,China;Organ Transplant Department,Tianjin First Central Hospital,Tianjin 300192,China;School of Medicine,Nankai University,Tianjin 300074,China;Tianjin Key Laboratory for Organ Transplantation,Tianjin First Central Hospital,Tianjin 300190,China)

机构地区：[1]天津市第一中心医院移植肿瘤科,天津300192 [2]天津市第一中心医院器官移植科,天津300192 [3]南开大学医学院,天津300074 [4]天津市第一中心医院器官移植重点实验室,天津300192

出　　处：《实用器官移植电子杂志》2024年第6期520-525,共6页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：天津市自然科学基金面上项目(21CYBJC01600)。

摘　　要：目的构建重复性和稳定性好的巴马小型猪肝移植无肝期动物模型。方法选用5只巴马小型猪,构建肝移植无肝期模型,为避免出现无肝期肠道淤血、循环衰竭,采用静脉-静脉转流模型,维持无肝期血压稳定以及加强术中麻醉与体液管理。观察并记录手术时间、出血量、补液量、转流流量及实验动物在血管阻断前、血管阻断时、静脉-静脉转流(venovenous bypass,VVB)开始后30 min、60 min、90 min和血管开放后30 min共6个时间点的血流动力学、肠损伤指标、肾损伤指标及内环境指标的变化情况。结果构建的小型猪肝移植无肝期静脉-静脉转流动物模型,静脉引流均较充分,主要表现为5只巴马小型猪均存活,且术中肠管颜色红润、蠕动正常,尿量正常。手术时间为(160±8)min,出血量约(158±32)ml,补液量为(1760±251)ml。与血管阻断前相比,血管阻断时动物心率明显加快,平均动脉压(mean arterial pressure,MAP)明显降低至(44±15)mmHg,血液pH值下降、乳酸升高。转流开始后巴马小型猪MAP上升,心率变慢,而血液pH值、乳酸变化不明显。整个实验期间,实验动物电解质变化不明显,而肌酐、肠脂肪酸结合蛋白缓慢升高。结论构建的巴马小型猪肝移植无肝期动物模型稳定且安全,能为进一步的静脉-静脉转流装置的验证等前临床实验提供有效的动物模型。Objective To establish a liver transplantation anhepatic model in Bama miniature pigs with high repeatability and stability.Methods Five Bama miniature pigs were selected to construct a liver transplantation model in the anhepatic stage.In order to avoid intestinal congestion and circulatory failure in the anhepatic stage,a veno-venous bypass model was adopted to maintain stable blood pressure in the anhepatic stage,and to enhance intraoperative anesthesia and fluid management.The changes of hemodynamic indexes of intestinal injury,kidney injury and internal environment were observed and recorded at 6 time points:30,60,90 min after VVB,before blood vessel occlusion and 30 min after vessel opening.Results The established veno-venous fluid transfer model of small pig liver transplantation in the anhepatic stage had adequate venous drainage.The main results showed that 5 Bama small pigs were all alive,and the intestinal tube color was rosy and the peristalsis was normal,and the urine volume was normal.The operation time was(160±8)min,the blood loss was(158±32)ml,and the fluid rehydration was(1760±251)ml.Compared with before vascular occlusion,the heart rate of the animals was significantly increased during vascular occlusion,the MAP was significantly decreased to(44±15)mmHg(1 mmHg=0.133 kPa),the blood pH was decreased,and the lactic acid was increased,heart rate slowed,and blood pH did not change significantly in lactic acid throughout the experiment,the experimental animals did not change significantly in electrolyte,while creatinine and intestinal fatty acid binding protein slowly increased.Conclusion The established Bama small porcine liver transplantation model is stable and safe,which can provide an effective animal model for further clinical trials such as validation of veno-venous transfer device.

关 键 词：肝移植 无肝期 动物模型 巴马小型猪 

分 类 号：R657.3[医药卫生—外科学] R-332[医药卫生—临床医学]