Liver regeneration investigated in a non-human primate model (Macaca mulatta)
Liver regeneration investigated in a non-human primate model (Macaca mulatta)
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DOI：
10.1016/s0168-8278(02)00262-3
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发表时间：
2002-11-01
影响因子：
25.7
通讯作者：
Theise, ND
中科院分区：
文献类型：
--
作者：
Gaglio, PJ;Liu, HF;Theise, ND
背景/目的：目前还没有研究人类肝再生的适当模型。我们探讨了研究肝再生的可行性，在一个遗传相似的物种的人，非人灵长类动物恒河猴。方法：五只动物进行了研究;两个进行了60%的肝切除术，一个进行了30%的肝切除术，和胆囊切除术单独进行了两个动物。在所有手术后的第1、2、7、149、21、30和60天进行腹腔镜引导或开放式肝活检。通过测量Ki-67，增殖细胞核抗原表达和有丝分裂指数，计算肝残体的表面积的变化和评估肝内生产的cytokines.Results：显着的肝再生诱导的动物进行了60%的肝切除术，术后21-30天之间达到高峰。在研究的所有其他动物中，再生最小。细胞因子的产生遵循类似的模式。最大肝再生与恢复表面积在liver residue.Conclusions：百分之六十的非人灵长类动物模型中肝切除诱导显着的肝再生，最大化21-30天后部分肝切除术，表明一个显着的种间差异相比，啮齿动物肝切除模型。恒河猴的部分肝切除模型可能允许进一步表征更接近人类的物种中的肝再生。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版，版权所有。
Background/Aims: An adequate model to study liver regeneration in humans is presently unavailable. We explored the feasibility of studying liver regeneration in a genetically similar species to man, the non-human primate Rhesus macaque.Methods: Five animals were studied; two underwent 60% hepatectomy, one underwent 30% hepatectomy, and cholecystectomy alone was performed on two animals. Laparoscopic-guided or open liver biopsies were performed on days 1, 2, 7, 149 21, 30 and 60 following all surgeries. Liver regeneration was evaluated by measuring Ki-67, proliferating cell nuclear antigen expression and mitotic index, calculating changes in the surface area of the liver remnant and assessing intrahepatic production of cytokines.Results: Significant liver regeneration was induced in the animals that underwent 60% hepatectomy, peaking between days 21-30 postoperatively. Regeneration was minimal in all other animals studied. Cytokine production followed a similar pattern. Maximal liver regeneration correlated with restoration of surface area in the liver remnant.Conclusions: Sixty percent hepatectomy in a non-human primate model induced significant liver regeneration, maximizing 21-30 days following partial hepatectomy, suggesting a significant interspecies difference when compared to a rodent hepatectomy model. A partial hepatectomy model in Rhesus macaques may allow further characterization of liver regeneration in a species closer to humans. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.