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细胞色素P450和脂氧合酶代谢产物对肾功能的影响

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function.

作者信息

Imig John D, Khan Md Abdul Hye

机构信息

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

出版信息

Compr Physiol. 2015 Dec 15;6(1):423-41. doi: 10.1002/cphy.c150009.

Abstract

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function.

摘要

花生四烯酸代谢产物具有多种生物学作用,包括对肾脏的影响,可改变肾血流动力学和肾小管转运过程。环氧化酶代谢产物是花生四烯酸酶促途径的产物,该途径在肾功能方面已得到广泛研究。花生四烯酸代谢的另外两条鲜为人知的酶促途径是脂氧合酶(LO)和细胞色素P450(CYP)途径。现在人们已经认识到LO和CYP代谢产物对肾血流动力学和肾小管转运过程的重要性。LO和CYP代谢产物具有改变肾血流量和肾小球滤过率的作用。近端和远端肾小管钠转运以及液体和电解质平衡也受到肾脏CYP和LO水平的显著影响。LO和CYP途径的代谢产物还具有肾脏作用,可影响血管和上皮细胞的肾脏炎症、增殖和凋亡过程。这些肾脏LO和CYP途径的作用是通过特定代谢产物的生成和细胞信号机制发生的。尽管LO和CYP代谢产物对肾脏生理的重要性和作用显而易见,但我们对这些脂质介质对肾功能的理解仍存在重大差距。未来需要开展研究来填补这些关于LO和CYP代谢产物对肾功能影响的重大空白。

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