Wang Yubang, Qin Heng, Zhang Chengxiang, Huan Fei, Yan Ting, Zhang Lulu
The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Molecules. 2015 Dec 29;21(1):E46. doi: 10.3390/molecules21010046.
This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.
本研究旨在探讨维生素A缺乏是否会改变大鼠组织中P - 糖蛋白（P - GP）的表达和功能，以及这些影响是否会影响维生素A缺乏大鼠体内药物的分布。我们通过给大鼠喂食不含维生素A的饲料12周来诱导维生素A缺乏大鼠。然后，通过定量逆转录聚合酶链反应（qRT - PCR）和蛋白质免疫印迹法（Western blot）评估Abcb1/P - GP的表达。qRT - PCR分析显示，海马体和肝脏中Abcb1a信使核糖核酸（mRNA）水平升高。在肾脏中，仅呈现上升趋势。海马体中Abcb1b mRNA水平升高，但在大脑皮层、肝脏和肾脏中降低。蛋白质免疫印迹结果与Abcb1b mRNA水平的变化高度一致。通过罗丹明123（Rho123）的组织分布和体液排泄来研究P - GP功能，结果表明，大脑皮层、肝脏和肾脏中的P - GP活性也与P - GP表达高度一致。还通过长春新碱的组织分布研究了药物分布的变化，结果显示维生素A缺乏大鼠所有指定组织中的药物分布均呈现显著上升趋势。总之，维生素A缺乏可能会改变大鼠组织中Abcb1/P - GP的表达和功能，并且这些改变可能通过增加组织蓄积来提高药物活性/毒性。
