Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.
Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.
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使用树鼩（Tupaia belangeri）作为肝移植的新型动物模型。
DOI：
10.1007/s11596-018-1985-z
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Zhang Jie
中科院分区：
文献类型：
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作者：
Tang Bo;Wu Tao;Xiao Shu Feng;Ge Jia Yun;Wei Dong;Li Chun Man;Wang Qiu Hong;Zeng Wang;Fu Bi Mang;Zhang Jie
肝移植是治疗终末期肝病最有效、最有前途的方法。然而，仍有进一步改进和创新的空间，例如减少缺血再灌注损伤、移植排斥反应和免疫耐受。一个好的肝移植动物模型对于肝移植研究的创新是必不可少的。虽然大鼠LT模型自上个世纪以来就已被使用，但它一直不是理想的模型，因为在大鼠中观察到的结果可能不适用于人类，因为这两个物种在遗传上彼此不同。本研究首次采用与灵长类动物关系密切的攀缘目树鼩（Tupaia belangeri）进行肝移植，并探讨其作为肝移植新模型的可能性。采用双袖套法对30只动物进行肝移植，观察移植成功率、存活率和免疫反应。受体手术时间平均为60 min，无肝期时间限制在20 min内。移植后存活3 d以上的动物有27只（90%）。未接受任何免疫抑制药物的13只动物在8天内死亡，主要是由于急性排斥反应（n=9），类似于人的反应，但不是实验大鼠。其余14只给予雷帕霉素的动物存活时间明显更长（38天），其中一半存活了60天，直到研究结束。我们的研究结果表明，在树鼩中进行LT可以获得高成功率和高存活率。更重要的是，树鼩具有与人类相似的免疫反应。此外，以往的基因组学研究发现，树鼩与人类共享更多的蛋白质。因此，树鼩可以作为一种较好的、经济的LT动物模型。
Liver transplantation (LT) is most effective and promising approach for end-stage liver disease. However, there remains room for further improvement and innovation, for example, to reduce ischemic reperfusion injury, transplant rejection and immune tolerance. A good animal model of LT is essential for such innovation in transplant research. Although rat LT model has been used since the last century, it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other. In this study, we for the first time performed LT using the tree shrew (Tupaia belangeri), a species in the Order Scandentia which is closely related with primates, and evaluated the possibility to adopt this species as a new model of LT. We performed LT on 30 animals using the two-cuff technique, examining the success rate, the survival rate and the immunological reaction. The recipient operation time was 60 min averagely, and we limited the time of the anhepatic phase within 20 min. Twenty-seven (90%) of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9), similar to the reaction in human but not in experimental rat. The rest 14 animals that were given rapamycin survived significantly longer (38 days) and half of them survived for 60 days until the end of the study. Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate. More importantly, the tree shrews share similar immunological reaction with human. In addition, previous genomics study found that the tree shrews share more proteins with human. In sum, the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.