Miyata Masaaki, Hayashi Kenjiro, Yamakawa Hiroki, Yamazoe Yasushi, Yoshinari Kouichi
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578; Department of Food Science and Technology, National Fisheries University, 2-7-1 Nagatahonmachi, Shimonoseki, Yamaguchi 759-6595, Japan.
Biol Pharm Bull. 2015;38(3):493-6. doi: 10.1248/bpb.b14-00640. Epub 2014 Dec 27.
Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.
抗菌药物治疗通过提高肝脏胆汁酸合成来增加胆汁酸池大小和肝脏胆汁酸浓度。然而,肠道胆汁酸吸收在胆汁酸池大小增加中的作用仍不清楚。为了确定肠道胆汁酸吸收是否有助于抗菌药物治疗的小鼠胆汁酸池增加,我们评估了胆汁酸转运蛋白水平和肠道胆汁酸吸收能力。在氨苄青霉素(ABPC)治疗的小鼠中,回肠顶端钠依赖性胆汁酸转运体(ASBT)的mRNA和蛋白水平显著增加,而小鼠中有机溶质转运体α(OSTα)的mRNA水平显著降低,但蛋白水平未降低。在用杆菌肽/新霉素/链霉素治疗的小鼠中也观察到胆汁酸转运体表达水平的类似变化。通过原位肠袢法评估肠道胆汁酸吸收能力。在ABPC治疗的小鼠中观察到牛磺鹅去氧胆酸的回肠吸收增加。这些结果表明,在用抗菌药物治疗的小鼠中,肠道胆汁酸吸收以ASBT依赖性方式升高。