体外肝细胞的制备及在药物开发中的应用

The Methods of liver Cell Preparations in vitro and Their Applications in Drug Development

体外肝细胞模型(主要是原代肝细胞培养)作为一种强有力的体外研究体系被广泛应用于化学异物的肝毒性研究。由于肝细胞具有Ⅰ相、Ⅱ相药物代谢酶和药物转运载体,肝细胞被应用于药代动力学领域的研究,如:动力学参数、清除率、种属间比较、酶抑制和诱导效应、药物转运载体、药物-药物相互作用等。体外肝细胞模型在毒理学领域也有广泛的应用,如:细胞毒性和基因毒性物质的筛选、化学保护剂的评价、特异性肝损伤及相关生化机制的测定等。到目前为止,体外肝细胞模型已在基础性研究和新药早期筛选中得到广泛应用。

In vitro liver cell models （mainly primary hepatocyte cultures）, served as the most powerful in vitro research system are widely used for the study of hepatotoxicity of xenobiotics. Maintenance of phase Ⅰ and phase Ⅱ xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, clearance, interspecies comparison, inhibition and induction effects, transporters and drug-drug interactions （DDIs）. In vitro cell models also have various applications in toxicology, screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanism induced by toxic compounds. To date, in vitro liver cell models have been widely used in basic research and screening procedure early in drug development.