肠外营养仔猪模型中药物代谢相关基因的肠道表达变化
Changes in the intestinal expression of drug metabolism-related genes in a piglet model of parenteral nutrition.
作者信息
Dai Li-Na, Zhao Yu-Ling, Jiang Lu, Yan Jun-Kai
机构信息
Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Rd, Shanghai, 200092, China.
Department of Urology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Nutr Metab (Lond). 2022 Mar 9;19(1):18. doi: 10.1186/s12986-022-00654-8.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
肠外营养（PN）可作为一种伴随口服药物的营养支持疗法，但PN对肠道药物代谢相关基因表达的影响尚不清楚。
方法
将12只接受PN 14天的巴马仔猪作为体内模型。通过蛋白质组学分析检测肠道药物代谢相关基因的变化。采用酶联免疫吸附测定法（ELISA）测定成纤维细胞生长因子19（FGF19）的血清水平，并使用小鼠回肠类器官检测FGF19对药物代谢相关基因表达的影响。
结果
PN组共鉴定出1063种差异表达蛋白。值得注意的是，PN组中两种药物转运蛋白（Abcb1和Abcc2）以及两种与谷胱甘肽相关的药物代谢酶——谷胱甘肽过氧化物酶（Gpx2）和谷胱甘肽S-转移酶（Gsta1）显著降低。PN组血清FGF19水平显著降低。体外使用重组FGF19处理可使类器官中Abcb1、Abcc2、Gpx2和Gsta1的表达呈剂量依赖性上调。
结论
我们的数据表明，在PN条件下肠道药物代谢相关基因显著失调，部分变化的基因归因于肠道来源的FGF19。
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