Li Xiao-Jun, Suo Ping, Wang Yan-Ni, Zou Liang, Nie Xiao-Li, Zhao Ying-Yong, Miao Hua
School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Front Pharmacol. 2024 Mar 8;15:1365802. doi: 10.3389/fphar.2024.1365802. eCollection 2024.
Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney. Along with increased oxidative stress, apoptosis, inflammation and tissue fibrosis drive the progressive loss of kidney function, affecting the glomerular filtration barrier and the tubulointerstitium. Recent studies have shown that AA and its active derivative eicosanoids play important roles in the regulation of physiological kidney function and the pathogenesis of kidney disease. These factors are potentially novel biomarkers, especially in the context of their involvement in inflammatory processes and oxidative stress. In this review, we introduce the three main metabolic pathways of AA and discuss the molecular mechanisms by which these pathways affect the progression of acute kidney injury (AKI), diabetic nephropathy (DN) and renal cell carcinoma (RCC). This review may provide new therapeutic targets for the identification of AKI to CKD continuum.
花生四烯酸（AA）是细胞膜脂质的主要成分。AA主要由三种酶代谢：环氧化酶（COX）、脂氧合酶（LOX）和细胞色素P450（CYP450）。酯化的AA被磷脂酶A水解成游离形式，然后由COX、LOX和CYP450进一步代谢为多种生物活性介质，包括前列腺素、脂氧素、血栓素、白三烯、羟基二十碳四烯酸和环氧二十碳三烯酸。线粒体氧化应激增加被认为是肾脏病理生理学的核心机制。随着氧化应激增加，细胞凋亡、炎症和组织纤维化导致肾功能逐渐丧失，影响肾小球滤过屏障和肾小管间质。最近的研究表明，AA及其活性衍生物类花生酸在生理肾功能调节和肾脏疾病发病机制中起重要作用。这些因素可能是新的生物标志物，特别是在它们参与炎症过程和氧化应激的情况下。在本综述中，我们介绍了AA的三种主要代谢途径，并讨论了这些途径影响急性肾损伤（AKI）、糖尿病肾病（DN）和肾细胞癌（RCC）进展的分子机制。本综述可能为识别AKI至CKD连续体提供新的治疗靶点。
