Fukueda Mikio, Ishizaki Naoki, Hamada Nobuo, Kadono Jun, Kaieda Mamoru, Nakamura Noboru, Komokata Teruo, Sakata Ryuzou
The Second Department of Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
Transplantation. 2006 Nov 27;82(10):1312-8. doi: 10.1097/01.tp.0000243360.64554.fa.
Auxiliary partial orthotopic liver transplantation (APOLT) has been an effective alternative in acute liver failure (ALF), but clinically several problems remain to be resolved. Thus, we attempt to establish an APOLT model for ALF using a large animal and demonstrate the validity of our model.
In experiment 1, we created an animal model of ALF using pig. ALF was induced by resection of 70% of the whole liver under total hepatic vascular exclusion (THVE). The duration of ischemia was 90 minutes. In experiment 2, we tried to make an APOLT model by using this ALF model as a recipient. That is, during 90 minutes of THVE, 70% hepatectomy and subsequent partial orthotopic transplantation was completed.
In experiment 1, six of seven pigs died within three days with jaundice and massive ascites. Based on microcirculatory disturbance of the remnant liver and hepatocellular necrosis, 70% hepatectomy with 90 minutes of THVE was considered a proper model of ALF. In experiment 2, six out of seven APOLT model animals survived more than four days. T. Bil levels in the APOLT model remained consistently within the normal range throughout the observation period. In immunohistochemistry, several labeled nuclei stained with Ki67 were identified in native liver of the APOLT model.
This APOLT procedure provided temporary liver function support and enabled the recipient to survive until the failing native liver had regenerated. Our APOLT model could be suitable and useful for understanding the role of APOLT in ALF.
辅助性部分原位肝移植(APOLT)已成为急性肝衰竭(ALF)的一种有效替代方法,但临床上仍有几个问题有待解决。因此,我们试图用大型动物建立一种用于ALF的APOLT模型,并证明我们模型的有效性。
在实验1中,我们用猪创建了ALF动物模型。通过在全肝血流阻断(THVE)下切除70%的全肝来诱导ALF。缺血时间为90分钟。在实验2中,我们试图以这个ALF模型作为受体来建立APOLT模型。也就是说,在90分钟的THVE期间,完成70%肝切除术及随后的部分原位肝移植。
在实验1中,7头猪中有6头在三天内死于黄疸和大量腹水。基于残余肝脏的微循环紊乱和肝细胞坏死,70%肝切除术加90分钟THVE被认为是一个合适的ALF模型。在实验2中,7只APOLT模型动物中有6只存活超过4天。在整个观察期内,APOLT模型中的总胆红素(T. Bil)水平一直保持在正常范围内。在免疫组织化学中,在APOLT模型的自体肝脏中发现了几个用Ki67染色的标记细胞核。
这种APOLT手术提供了临时肝功能支持,使受体能够存活到衰竭的自体肝脏再生。我们的APOLT模型可能适用于并有助于理解APOLT在ALF中的作用。