Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
J Cell Physiol. 2014 May;229(5):599-606. doi: 10.1002/jcp.24482.
Liver regeneration after injury occurs in many mammals. Rat liver regenerates after partial hepatectomy over a period of 2 weeks while human liver regeneration takes several months. Notwithstanding this enormous difference in time-scales, with new data from five human live liver transplant donors, we show that a mathematical model of rat liver regeneration can be transferred to human, with all biochemical interactions and signaling unchanged. Only six phenomenological parameters need change, and three of these parameter changes are rescalings of rate constants by the ratio of human lifespan to rat lifespan. Data from three donor subjects with approximately equal resections were used to fit the three parameters and the data from the other two donor subjects was used to independently verify the fit.
肝脏在受伤后会进行再生。在两周的时间内，大鼠的肝脏可以在部分肝切除术后再生，而人类的肝脏再生则需要几个月的时间。尽管在时间尺度上存在如此巨大的差异，但通过对五名活体肝移植供体的新数据进行分析，我们表明，大鼠肝脏再生的数学模型可以转移到人类身上，其中所有生化相互作用和信号传递都保持不变。只有六个现象学参数需要改变，其中三个参数的改变是通过将人类寿命与大鼠寿命的比值对速率常数进行重新缩放。使用来自三个供体的具有大致相等切除量的数据来拟合三个参数，并且使用来自另外两个供体的数据来独立地验证拟合。
