Changes in the intestinal expression of drug metabolism-related genes in a piglet model of parenteral nutrition.
Changes in the intestinal expression of drug metabolism-related genes in a piglet model of parenteral nutrition.
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仔猪肠外营养模型肠道药物代谢相关基因表达变化
DOI：
10.1186/s12986-022-00654-8
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发表时间：
2022-03-09
影响因子：
4.5
通讯作者：
Yan JK
中科院分区：
文献类型：
--
作者：
Dai LN;Zhao YL;Jiang L;Yan JK
肠外营养（PN）可以作为一种营养支持治疗伴随口服药物，但PN对肠道药物代谢相关基因表达的影响仍然未知。12头接受PN 14天的巴马仔猪用作体内模型。通过蛋白质组学分析检测肠道药物代谢相关基因的变化。通过ELISA测定成纤维细胞生长因子19（FGF 19）的血清水平，并使用小鼠回肠类器官检查FGF 19对药物代谢相关基因表达的影响。PN组共鉴定出1063个差异表达蛋白。值得注意的是，PN组中两种药物转运蛋白（Abcb 1和Abcc 2）沿着两种谷胱甘肽相关药物代谢酶谷胱甘肽过氧化物酶（Gpx 2）和谷胱甘肽S-转移酶（Gsta 1）显著降低。PN组血清FGF 19水平显著降低。在体外用重组FGF 19处理剂量依赖性地上调类器官中Abcb 1、Abcc 2、Gpx 2和Gsta 1的表达。 我们的数据表明，肠道药物代谢相关基因在PN下显著失调，并且一些改变的基因归因于肠源性FGF 19。
Parenteral nutrition (PN) may serve as a nutritional supportive therapy accompanied by oral medication, but the effect of PN on intestinal expression of drug metabolism-related genes remains unknown. Twelve Bama piglets receiving PN for 14 days were used as in vivo model. Changes in intestinal drug metabolism-related genes were examined by proteomic analysis. Serum levels of fibroblast growth factor 19 (FGF19) were determined by ELISA, and the effect of FGF19 on the expression of drug metabolism-related genes was examined using murine ileum organoids. A total of 1063 differentially expressed proteins were identified in PN group. Of note, two drug transporters (Abcb1 and Abcc2) were significantly decreased in PN group, along with two glutathione-related drug-metabolizing enzymes, glutathione peroxidase (Gpx2) and glutathione S-transferase (Gsta1). Serum FGF19 levels were dramatically reduced in PN group. Treatment with recombinant FGF19 in vitro dose-dependently up-regulated the expression of Abcb1, Abcc2, Gpx2 and Gsta1 in organoids. Our data indicated that intestinal drug metabolism-related genes were significantly dysregulated under PN, and some of the changed genes were attributed to gut-derived FGF19.
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