Shang H, Yang J, Liu Y, Wei H
Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, P. R. China.
Xenobiotica. 2009 Jun;39(6):423-9. doi: 10.1080/00498250902825363.
Pig or minipig cytochrome P450 (CYP) 3A isozymes have been proven to be a good model of human drug metabolism, and human CYP3A seems to be well modelled by pig or minipig CYP3A29. We studied CYP3A29 mRNA expression in ten tissues (liver, duodenum, kidney, adrenal gland, skin, brain, lung, testis, uterus and ovary) in different age groups of Bama miniature pig by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In adult pig (4 and 6 months old), the most relative expression by normalization to beta-actin of CYP3A29 mRNAs of tissues is in liver; then in duodenum, skin and kidney. Values of CYP3A29 in the extrahepatic tissues except for duodenum are very low compared with that in liver. In new-borns the mean CYP3A29 expression in duodenum was higher than that in liver, and the expression in skin was very low while high in 40 days, 4 months and 6 months age groups. For different ages, the increased CYP3A29 expression in liver and duodenum was detected with age. The effective CYP3A29 induction in liver was also detected by rifampin oral intubation. Apparent interindividual variability of CYP3A29 mRNA expression in Bama miniature pigs was detected. This work will broaden the understanding of the physiological functions of CYP3A29 in miniature pig, and promote Bama miniature pig's application in pharmacological and toxicological studies.
猪或小型猪的细胞色素P450(CYP)3A同工酶已被证明是人类药物代谢的良好模型,并且猪或小型猪的CYP3A29似乎能很好地模拟人类CYP3A。我们通过实时逆转录聚合酶链反应(RT-PCR)研究了不同年龄组巴马小型猪的10种组织(肝脏、十二指肠、肾脏、肾上腺、皮肤、大脑、肺、睾丸、子宫和卵巢)中CYP3A29 mRNA的表达。在成年猪(4个月和6个月龄)中,以β-肌动蛋白标准化后,各组织CYP3A29 mRNA的相对表达量以肝脏中最高;其次是十二指肠、皮肤和肾脏。除十二指肠外,肝外组织中CYP3A29的值与肝脏中的相比非常低。在新生仔猪中,十二指肠中CYP3A29的平均表达高于肝脏,皮肤中的表达非常低,而在40天、4个月和6个月龄组中较高。对于不同年龄,肝脏和十二指肠中CYP3A29的表达随年龄增加。通过利福平口服插管也检测到肝脏中CYP3A29的有效诱导。检测到巴马小型猪中CYP3A29 mRNA表达存在明显的个体间差异。这项工作将拓宽对小型猪中CYP3A29生理功能的理解,并促进巴马小型猪在药理和毒理学研究中的应用。