Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.
Front Endocrinol (Lausanne). 2024 Feb 15;15:1304547. doi: 10.3389/fendo.2024.1304547. eCollection 2024.
In recent years, numerous experimental studies have underscored the pivotal role of soluble epoxide hydrolase (sEH) in renal diseases, demonstrating the reno-protective effects of sEH inhibitors. The nexus between sEH and renal-associated diseases has garnered escalating attention. This review endeavors to elucidate the potential molecular mechanisms of sEH in renal diseases and emphasize the critical role of sEH inhibitors as a prospective treatment modality. Initially, we expound upon the correlation between sEH and Epoxyeicosatrienoic acids (EETs) and also addressing the impact of sEH on other epoxy fatty acids, delineate prevalent EPHX2 single nucleotide polymorphisms (SNPs) associated with renal diseases, and delve into sEH-mediated potential mechanisms, encompassing oxidative stress, inflammation, ER stress, and autophagy. Subsequently, we delineate clinical research pertaining to sEH inhibition or co-inhibition of sEH with other inhibitors for the regulation of renal-associated diseases, covering conditions such as acute kidney injury, chronic kidney diseases, diabetic nephropathy, and hypertension-induced renal injury. Our objective is to validate the potential role of sEH inhibitors in the treatment of renal injuries. We contend that a comprehensive comprehension of the salient attributes of sEH, coupled with insights from clinical experiments, provides invaluable guidance for clinicians and presents promising therapeutic avenues for patients suffering from renal diseases.
近年来,大量的实验研究强调了可溶性环氧化物水解酶 (sEH) 在肾脏疾病中的关键作用,证明了 sEH 抑制剂的肾保护作用。sEH 与肾脏相关疾病之间的联系引起了越来越多的关注。本综述旨在阐明 sEH 在肾脏疾病中的潜在分子机制,并强调 sEH 抑制剂作为一种有前途的治疗方式的关键作用。首先,我们阐述了 sEH 与 Epoxyeicosatrienoic acids (EETs) 的相关性,并讨论了 sEH 对其他环氧脂肪酸的影响,描述了与肾脏疾病相关的常见 EPHX2 单核苷酸多态性 (SNPs),并探讨了 sEH 介导的潜在机制,包括氧化应激、炎症、内质网应激和自噬。随后,我们描述了与 sEH 抑制或与其他抑制剂联合抑制 sEH 以调节肾脏相关疾病的临床研究,涵盖急性肾损伤、慢性肾脏病、糖尿病肾病和高血压引起的肾损伤等疾病。我们的目的是验证 sEH 抑制剂在治疗肾损伤中的潜在作用。我们认为,全面了解 sEH 的重要属性,并结合临床实验的见解,为临床医生提供了宝贵的指导,并为患有肾脏疾病的患者提供了有前途的治疗途径。