Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in ApoE knockout and C57BL/6 mice

被引:8
作者
Håkansson, P [1 ]
Andersson, I [1 ]
Nyström, S [1 ]
Löfgren, L [1 ]
Amrot, LF [1 ]
Li, H [1 ]
机构
[1] AstraZeneca R&D, Dept Integrat Pharmacol, Discovery, SE-43183 Molndal, Sweden
关键词
ASBT; bile acids; ILBP; mice; ontogenesis; (75)SeHCAT;
D O I
10.1080/003655202320378301
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Although apoE-/- mice are characterized by hypercholesterolemia, the bile acid enterohepatic circulation, which plays a crucial role in cholesterol homeostasis, has not been examined in these mice. The differences between apoE-/- and C57BL/6 mice in expression of the ileal ASBT and ILBP and in intestinal bile acid absorption were studied. Methods: The intestinal tissues of the fetal, neonatal and post-weaning mice were processed for immunohistochemistry. Body retention and fecal excretion of 75 SeHCAT were measured. The bile acid pool size and its composition were analysed by HPLC. Results: In apoE-/- and C57BL/6 mice, the bile acid pool size was 75 +/- 13 and 78 +/- 13 mumol/100 g body weight, respectively, while the ratio of cholic acid/beta-muricholi c acid was 1.8 +/- 0.3 and 1.4 +/- 0. 3 (P < 0.05), respectively. The daily body retention of 75 SeHCAT was 48% +/- 1.8% in C57 black mice and 58.4% +/- 2.7% in apoE-/- mice (P < 0.05). In both mouse strains, ASBT expression in the small intestine was found in the near-term fetal and post-weaning mice, while ILBP expression was found in all postnatal mice. In the post-weaning mice, ILBP expression was limited to the distal 25%-30% of the small intestine, while ASBT expression was limited to the distal 18%. Conclusions: The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice.
引用
收藏
页码:1089 / 1096
页数:8
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