The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo.
The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo.
复制标题
维生素A缺乏大鼠P-糖蛋白表达和功能的改变及体内药物配置的影响
DOI：
10.3390/molecules21010046
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发表时间：
2015-12-29
期刊：
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Wang Y;Qin H;Zhang C;Huan F;Yan T;Zhang L
本研究旨在探讨维生素A缺乏是否会改变大鼠组织中P-GP的表达和功能，以及这种影响是否会影响维生素A缺乏大鼠体内药物分布。我们通过给缺乏维生素A的大鼠12周的无维生素A饮食来诱导它们。然后通过qRT-PCR和Western blot检测Abcb 1/P-GP的表达。qRT-PCR分析显示海马和肝脏中Abcb 1a mRNA水平增加。在肾脏中，仅呈上升趋势。Abcb 1b mRNA在海马中表达增加，而在大脑皮质、肝脏和肾脏中表达降低。Western blot结果与Abcb 1b mRNA水平的变化相一致。通过罗丹明123（Rho 123）的组织分布和体液排泄研究了P-GP的功能，结果表明P-GP活性与P-GP在大脑皮质、肝脏和肾脏中的表达也有很好的一致性。通过长春新碱的组织分布考察了药物分布的变化，结果显示在维生素A缺乏大鼠的所有指示组织中均呈显著上升趋势。总之，维生素A缺乏可能会改变Abcb 1/P-GP在大鼠组织中的表达和功能，这种改变可能会通过增加组织蓄积来增加药物活性/毒性。
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.
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影响因子：
3.9
作者：
Chen W;Chen G
通讯作者：
Chen G
影响因子：
5.8
作者：
Chen, Yakun;Tang, Yong;Guo, Changxiong;Wang, Jiuhui;Boral, Debasish;Nie, Daotai
通讯作者：
Nie, Daotai
影响因子：
3.3
作者：
Liu, Y.;Liu, H.;Wang, G.
通讯作者：
Wang, G.
影响因子：
8
作者：
Lecureur, V;Thottassery, JV;Schuetz, JD
通讯作者：
Schuetz, JD
影响因子：
1.8
作者：
Olivares, A.;Reya, A. I.;Lopez-Bote, C. J.
通讯作者：
Lopez-Bote, C. J.