摘要
Kelch样ECH相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)-核转录因子E2相关因子2(nuclear factor erythroid 2 related factor 2,Nrf2)-抗氧化响应元件(antioxidant response element, ARE)作为重要的抗氧化应激通路,通过调控氧化应激,能够多方面调节DKD发病机制,改善DKD。益气活血类中药能够激活Keap1-Nrf2-ARE信号通路、下调活性氧含量、调控Keap1-Nrf2解离、促进Nrf2入核、激活ARE抗氧化应激元件以及调节下游抗氧化蛋白因子表达,从而改善DKD。目前,仍缺乏以Keap1-Nrf2-ARE通路为介导从细胞、分子及上游基因调控层面对糖尿病及其并发症的研究,且益气活血类药物的相互作用及对Keap1-Nrf2-ARE信号通路的影响尚未明确。今后需针对DKD氧化应激的病理机制,进一步加强临床试验及动物实验,积极寻找具有促进Keap1-Nrf2解离、Nrf2入核等作用的激动剂,以激活Keap1-Nrf2-ARE通路,为临床防治DKD药物的发掘提供方向。
Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE) as an important antioxidant stress pathway, by regulating oxidative stress, can regulate the pathogenesis of DKD in many ways and improve DKD.The traditional Chinese medicines of Yiqi Huoxue can activate the Keap1-Nrf2-ARE signaling pathway, down-regulate the content of reactive oxygen species, regulate the dissociation of Keap1-Nrf2,promote the entry of Nrf2 into the nucleus, activate the ARE anti-oxidative stress elements, and regulate the expression of downstream antioxidant protein factors, thus to improve the clinical symptoms of DKD.At present, there is still a lack of research on diabetes and its complications from the cellular, molecular and upstream gene regulation levels mediated by the Keap1-Nrf2-ARE pathway.And the interaction of Yiqi Huoxue drugs and their effects on the Keap1-Nrf2-ARE signaling pathway are not clear yet.In the future, it is necessary to further strengthen clinical trials and animal experiments for the pathological mechanism of DKD oxidative stress, and actively search for agonists that can promote the dissociation of Keap1-Nrf2 and the entry of Nrf2 into the nucleus, so as to activate the Keap1-Nrf2-ARE pathway, and provide directions for the discovery of clinical drugs for the prevention and treatment of DKD.
作者
周吉
王子晨
阴永辉
ZHOU Ji;WANG Zichen;YIN Yonghui(Shandong University of Traditional Chinese Medicine,Ji′nan Shandong China 250355;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji′nan Shandong China 250014)
出处
《中医学报》
CAS
2022年第4期742-750,共9页
Acta Chinese Medicine
基金
国家自然科学基金项目(81503572)
山东省自然科学基金项目(ZR2015HL107)
山东省中医药科技发展计划项目(2015-002)
山东中医药大学科研创新团队项目(2018-10)。
