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维生素 A 缺乏导致大鼠肾脏脂质外排途径失调。

Vitamin A deficiency results in dysregulation of lipid efflux pathway in rat kidney.

机构信息

Department of Nephroimmunology, Children's Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400014, People's Republic of China.

出版信息

Pediatr Nephrol. 2010 Aug;25(8):1435-44. doi: 10.1007/s00467-010-1532-z. Epub 2010 May 18.

DOI:10.1007/s00467-010-1532-z
PMID:20480185
Abstract

The mechanisms of action of vitamin A deficiency (VAD) on lipid metabolism in the rat kidney were investigated in adult female rats and their offspring. The rats were randomized into three groups: (1) control, in which the mother and offspring received a normal diet (4000 retinol IU/kg diet) for 8 weeks; (2) VAD group, in which the mothers and offspring received a VAD diet (400 retinol IU/kg diet) for 8 weeks; (3) vitamin A-refed group, in which a group of pups on a VAD diet for 8 weeks received a complete diet (6500 retinol IU/kg diet) for 15 days. The lipid metabolism of the offsprings' kidneys and its relation to the expression of apolipoprotein B100 (Apo-B100), liver X receptor alpha (LXRalpha), and retinoid X receptor-alpha/beta (RXRalpha/beta) mRNA was analyzed. VAD was found to alter renal lipid metabolism and its immune environment due to the expression of Apo-B100. Compared with the control, VAD rats had significantly higher levels of transforming growth factor-beta 1 and lower levels of ABCA1, a key gene involved in cholesterol efflux and tissue lipid homeostasis. The expression of LXRalpha and RXRalpha/beta mRNA also decreased in the VAD rat kidney. Vitamin A refeeding reversed all of the changes. Lipid metabolism involved in renal reverse cholesterol transport may be mediated by decreasing the signaling through the ABCA1 cholesterol efflux pathway, which is significantly modified in kidneys of vitamin A-deficient rats.

摘要

维生素 A 缺乏症 (VAD) 对成年雌性大鼠及其后代肾脏脂质代谢的作用机制进行了研究。将大鼠随机分为三组:(1)对照组,母亲和后代接受正常饮食(4000 视黄醇 IU/kg 饮食)8 周;(2)VAD 组,母亲和后代接受 VAD 饮食(400 视黄醇 IU/kg 饮食)8 周;(3)维生素 A 再喂养组,一组接受 VAD 饮食 8 周的幼鼠接受完全饮食(6500 视黄醇 IU/kg 饮食)15 天。分析了后代肾脏的脂质代谢及其与载脂蛋白 B100(Apo-B100)、肝 X 受体α(LXRα)和视黄醇 X 受体-α/β(RXRα/β)mRNA 表达的关系。VAD 通过 Apo-B100 的表达改变了肾脏的脂质代谢及其免疫环境。与对照组相比,VAD 大鼠的转化生长因子-β1 水平显著升高,载脂蛋白 A1(参与胆固醇外排和组织脂质稳态的关键基因)水平显著降低。LXRα 和 RXRα/β mRNA 的表达在 VAD 大鼠肾脏中也降低。维生素 A 再喂养逆转了所有这些变化。涉及肾脏胆固醇逆转运的脂质代谢可能通过降低 ABCA1 胆固醇外排途径的信号传导来介导,该途径在维生素 A 缺乏大鼠的肾脏中显著改变。

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本文引用的文献

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J Nutr Sci Vitaminol (Tokyo). 2009 Jun;55(3):208-14. doi: 10.3177/jnsv.55.208.
2
Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney.肾质量减少导致残余肾中脂质蓄积和脂质调节蛋白失调。
Am J Physiol Renal Physiol. 2009 Jun;296(6):F1297-306. doi: 10.1152/ajprenal.90761.2008. Epub 2009 Apr 8.
3
Effect of nutritional vitamin A deficiency on lipid metabolism in the rat heart: Its relation to PPAR gene expression.
Environ Sci Pollut Res Int. 2015 Apr;22(8):5751-5. doi: 10.1007/s11356-015-4144-0. Epub 2015 Jan 29.
4
Vitamin a deficiency and alterations in the extracellular matrix.维生素A缺乏与细胞外基质的改变。
Nutrients. 2014 Nov 10;6(11):4984-5017. doi: 10.3390/nu6114984.
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Nutrition. 2009 Jul-Aug;25(7-8):828-38. doi: 10.1016/j.nut.2009.01.008. Epub 2009 Apr 1.
4
The RXR agonists PA024 and HX630 have different abilities to activate LXR/RXR and to induce ABCA1 expression in macrophage cell lines.视黄酸X受体(RXR)激动剂PA024和HX630在巨噬细胞系中激活肝X受体(LXR)/视黄酸X受体(RXR)以及诱导ATP结合盒转运体A1(ABCA1)表达的能力不同。
Biochem Pharmacol. 2008 Oct 15;76(8):1006-13. doi: 10.1016/j.bcp.2008.08.005. Epub 2008 Aug 12.
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