Ogura Jiro, Fujikawa Asuka, Maruyama Hajime, Kobayashi Masaki, Itagaki Shirou, Iseki Ken
Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University.
Yakugaku Zasshi. 2011 Mar;131(3):453-62. doi: 10.1248/yakushi.131.453.
Alteration of P-glycoprotein (P-gp) expression influences the pharmacokinetics of P-gp substrates after intestinal ischemia-reperfusion (I/R). Fasting before intestinal I/R affects intestinal I/R injury. However, the effect of fasting on the alteration of P-gp expression after intestinal I/R has not been clarified. We previously reported that P-gp expression was altered after intestinal I/R following feeding. In the present study, we investigated the expression of P-gp after intestinal I/R following 16-h fasting. The mdr1a levels were decreased at 6 h in the jejunum, at 1 h in the ileum, at 6 and 24 h in the liver and at 6 h in the kidney. The mdr1b levels were decreased at 6 h in the ileum and at 1 and 6 h in the kidney. The mdr1b level in the liver was increased at 1 and 6 h. The expression of P-gp was decreased at 6 h in the jejunum, at 1, 6 and 24 h in the ileum, and at 6 h in the kidney. These alterations were different to those after intestinal I/R following feeding. In particular, the decrease in P-gp expression in the 16-h fasting I/R rats occurred at an early time during reperfusion compared with that in the feeding I/R rats. In conclusion, feeding condition affects the alteration of P-gp expression after intestinal I/R. Therefore, it is important to understand the patient's feeding condition for safe drug therapy.
P-糖蛋白(P-gp)表达的改变会影响肠道缺血再灌注(I/R)后P-gp底物的药代动力学。肠道I/R前禁食会影响肠道I/R损伤。然而,禁食对肠道I/R后P-gp表达改变的影响尚未阐明。我们之前报道过喂食后肠道I/R会导致P-gp表达改变。在本研究中,我们调查了禁食16小时后肠道I/R时P-gp的表达情况。多药耐药蛋白1a(mdr1a)水平在空肠6小时、回肠1小时、肝脏6小时和24小时以及肾脏6小时时降低。多药耐药蛋白1b(mdr1b)水平在回肠6小时以及肾脏1小时和6小时时降低。肝脏中mdr1b水平在1小时和6小时时升高。P-gp表达在空肠6小时、回肠1小时、6小时和24小时以及肾脏6小时时降低。这些改变与喂食后肠道I/R后的改变不同。特别是,与喂食I/R大鼠相比,禁食16小时的I/R大鼠中P-gp表达的降低在再灌注早期就出现了。总之,喂食状况会影响肠道I/R后P-gp表达的改变。因此,了解患者的喂食状况对于安全的药物治疗很重要。