衣康酸治疗肾脏疾病的研究进展

Progress of Itaconate in the Treatment of Renal Diseases

衣康酸作为IRG1编码的顺式乌头酸脱羧酶催化形成的代谢物,在巨噬细胞中生成,具有免疫调节功能,可以抑制过度炎症并激活Nrf2抗炎抗氧化通路。天然衣康酸不是绝对的免疫抑制剂,但衣康酸衍生物具有更强的Nrf2诱导性和更强的炎症抑制性,已有研究发现衣康酸及其衍生物可治疗肿瘤、退行性神经病变和多类炎性疾病。因高血流高耗氧的生理特性,肾脏易暴露于各种刺激因子并发生缺血缺氧损伤,近年多项研究发现衣康酸在治疗肾脏疾病方面的潜力。本综述讨论了衣康酸及衍生物对改善急性肾损伤、慢性肾脏病和狼疮性肾炎的研究进展,并总结了相关机制,包括激活Nrf2抗炎抗氧化通路、调节巨噬细胞免疫活动以及抑制核因子NF-κB和炎症小体NLRP3下游炎性因子释放。

Itaconate is produced in macrophages as a metabolite catalysed by IRG1-encoded cis-aconitate de-carboxylase and has immunomodulatory properties, inhibiting excessive inflammation and acti-vating the Nrf2 anti-inflammatory antioxidant pathway. Natural itaconate is not an absolute immu-nosuppressant, but itaconate derivatives have stronger ability to induce Nrf2 and more potent in-flammatory inhibitory properties than natural itaconate, and itaconate and its derivatives have been found to be useful in the treatment of tumours, degenerative neuropathies, and multiple types of inflammatory diseases. Due to the physiological characteristics of high blood flow and high oxy-gen consumption, the kidneys are easily exposed to a variety of irritating factors and undergo is-chemic and hypoxic injuries. In recent years, a number of studies have found that itaconate has the potential to be used in the treatment of renal diseases. This review discusses the research progress of itaconate and derivatives in ameliorating acute kidney injury, chronic kidney disease and lupus nephritis, and summarizes the related mechanisms, including activation of the Nrf2 pathway, mod-ulation of macrophage immune activity, and inhibition of inflammatory factor release downstream of NF-κB and NLRP3.