凝胶包埋大鼠肝细胞用于醋氨酚肝毒性研究

Test on hepatotoxicity of acetaminophen using gel entrapment culture of rat hepatocytes

以传统的多孔板贴壁培养为比较对象,采用醋氨酚为肝毒性药物模型,评价胶原凝胶包埋培养大鼠肝细胞用于药物肝毒性研究的可行性.结果发现,虽然多孔板培养和凝胶包埋培养肝细胞均表现出对醋氨酚肝毒性的浓度依赖性,但前者对毒性的敏感程度比后者小得多.在同样低浓度(2.5 mmol/L)的醋氨酚作用24 h后,胶原凝胶包埋的细胞活率下降到了对照组的35%,单层贴壁培养细胞的活率仅下降到了对照组的88%;以尿素和白蛋白合成能力表征的肝功能也出现同样趋势.此外,N-乙酰半胱氨酸(NAC)与甘草酸(GA)与醋氨酚一起加到培养基中能显著抑制醋氨酚导致的肝毒性,进一步说明凝胶包埋培养肝细胞可以反映保肝药物的临床作用.

Compared with monolayer culture, collagen gel entrapment culture of hepatoeytes was evaluated as a hepatotoxicity model through testing on the hepatotoxicity of acetaminophen. Although both hepatocyte cultures showed concentration-dependent hepatotoxicity of acetaminophen, monolayer hepatocytes were less sensitive than gel entrapped hepatocytes. When exposed to the same low concentration of acetaminophen （2.5 mmol/L） for 24 h, gel entrapped hepatocytes presented much lower viability than monolayer hepatocytes and similar trend existed in urea genesis and albumin synthesis. Moreover, addition of N-acetylcysteine or glycyrrhizic acid together with acetaminophen reduced the hepatotoxicity of acetaminophen, which illustrated the feasibility of gel entrapment culture of hepatocytes as a hepatotoxicity model to reflect the situation of a hepatoprotective drug in vivo.