Chimeric mice with humanized livers: a unique tool for in vivo and in vitro enzyme induction studies.
Chimeric mice with humanized livers: a unique tool for in vivo and in vitro enzyme induction studies.
复制标题
DOI：
10.3390/ijms15010058
复制
发表时间：
2013-12-20
影响因子：
5.6
通讯作者：
Tateno C
中科院分区：
文献类型：
--
作者：
Kakuni M;Yamasaki C;Tachibana A;Yoshizane Y;Ishida Y;Tateno C
我们进行了体内和体外研究，以确定人细胞色素P450（CYP）的诱导，使用具有人源化肝脏的嵌合小鼠（PXB-小鼠®）和从PXB-小鼠分离的人肝细胞（PXB-细胞），其来源于相同供体。对于体内研究，用3-甲基胆蒽（3-MC，2或20 mg/kg）或利福平（0.1或10 mg/kg）注射PXB小鼠4天。对于体外研究，将PXB细胞与3-MC（10、50或250 ng/mL）或利福平（5或25 μg/mL）孵育。20 mg/kg 3-MC（Cmax，12.2 ng/mL）和10 mg/kg利福平（Cmax，6.9 μg/mL）组PXB小鼠肝脏中的CYP 1A 1和1A 2以及CYP 3A 4 mRNA表达水平分别显著升高。250 ng/mL 3-MC的PXB细胞中CYP 1A 1 mRNA表达水平显著增加，表明敏感性低于体内。50 ng/mL的3-MC和5 μg/mL的利福平分别使CYP 1A 2和CYP 3A 4 mRNA表达水平显著升高，表明体内和体外研究的敏感性相似。总之，PXB-小鼠和PXB-细胞提供了一个强大的模型，作为体内和体外人类代谢酶诱导研究之间的中间体。
We performed in vivo and in vitro studies to determine the induction of human cytochrome P450 (CYP) using chimeric mice with humanized liver (PXB-mice®) and human hepatocytes isolated from the PXB-mice (PXB-cells), which were derived from the same donor. For the in vivo study, PXB-mice were injected with 3-methylcholanthrene (3-MC, 2 or 20 mg/kg) or rifampicin (0.1 or 10 mg/kg) for four days. For the in vitro study, PXB-cells were incubated with 3-MC (10, 50, or 250 ng/mL) or with rifampicin (5 or 25 μg/mL). The CYP1A1 and 1A2, and CYP3A4 mRNA expression levels increased significantly in the PXB-mouse livers with 20 mg/kg of 3-MC (Cmax, 12.2 ng/mL), and 10 mg/kg rifampicin (Cmax, 6.9 μg/mL), respectively. The CYP1A1 mRNA expression level increased significantly in PXB-cells with 250 ng/mL of 3-MC, indicating lower sensitivity than in vivo. The CYP1A2 and CYP3A4 mRNA expression levels increased significantly with 50 ng/mL of 3-MC, and 5 μg/mL of rifampicin, respectively, which indicated that the sensitivities were similar between in vivo and in vitro studies. In conclusion, PXB-mice and PXB-cells provide a robust model as an intermediate between in vivo and in vitro human metabolic enzyme induction studies.
登录
查看更多内容
影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
4.9
作者：
Polk, RE;Brophy, DF;Stein, DS
通讯作者：
Stein, DS
影响因子：
6
作者：
Asahina, K;Sato, H;Yoshizato, K
通讯作者：
Yoshizato, K
DOI：
10.1006/bbrc.2001.4464
发表时间：
2001-03-16
影响因子：
3.1
作者：
Sugihara, K;Kitamura, S;Fujii-Kuriyama, Y
通讯作者：
Fujii-Kuriyama, Y
影响因子：
3.9
作者：
Hasegawa, Maki;Tahara, Harunobu;Ushiki, Junko
通讯作者：
Ushiki, Junko