基于细胞焦亡与铁死亡的中药治疗糖尿病肾病机制研究进展

Study on the mechanism of treating diabetic nephropathy with Chinese medicine based on scorch death and iron deathprogress of investigation

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中文摘要：糖尿病肾病(diabetic kidney disease,DKD)是导致慢性肾脏病(chronic kidney disease,CKD)和终末期肾病(end-stage renal disease,ESRD)的重要因素,其发病率高,治疗困难,阻断或延缓其病程进展十分重要.近年来,细胞焦亡和铁死亡是已被发现参与DKD发病机制的重要的程序性细胞死亡(programmed cell death,PCD)新方式.研究表明,细胞焦亡主要通过NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体复合物诱发肾脏炎症反应和氧化应激参与或加速DKD的发生与发展.铁死亡参与DKD发病过程可能与谷胱甘肽过氧化物酶 4(glutathione peroxidase 4,GPX4)、缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血红素加氧酶-1(heme oxygenase-1,HO-1)及核因子 E2 相关因子 2(nuclear factor E2-related factor 2,Nrf2)等因素有关.现代研究证明,中药及其单体成分可以通过调控细胞焦亡抑制肾脏炎症反应、氧化应激及抗肾纤维化而延缓DKD病程,亦可通过抑制肾脏细胞铁死亡而改善肾小管、肾小球损伤及抗肾纤维化来延缓DKD进展.从细胞焦亡与铁死亡角度探讨中药治疗DKD的发病机制,将为深入研究DKD发病机制,指导临床应用中药及研发新药来延缓DKD病程提供研究思路和理论依据.

外文摘要：Diabetic kidney disease(DKD)is an important factor leading to chronic kidney disease(CKD)and end-stage renal disease(ESRD),which is highly prevalent and difficult to treat,and it is very important to block or slow down its progression.In recent years,pyroptosis and ferroptosis are new important modes of programmed cell death(PCD)that have been found to be involved in the pathogenesis of DKD.Studies have shown that cell pyroptosis is involved in or exacerbates the development of DKD mainly through NLRP3 inflammatory vesicle complex-induced renal inflammatory response and oxidative stress.The involvement of iron death in the pathogenesis of DKD may be related to glutathione peroxidase 4(GPX4),hypoxia-inducible factor-1α(HIF-1α),heme oxygenase-1(HO-1)and nuclear factor E2-related factor 2(Nrf2).Modern studies have demonstrated that traditional Chinese medicine(TCM)and its monomer components can slow down the progression of DKD by regulating cellular pyroptosis,inhibiting renal inflammation,oxidative stress and anti-renal fibrosis,and can also slow down the progression of DKD by inhibiting renal cellular iron death and improving tubular and glomerular injury and anti-renal fibrosis.Discussing the pathogenesis of DKD in TCM based on cellular pyroptosis and iron death will provide ideas and theoretical basis for in-depth study of the pathogenesis of DKD,wich can guide the clinical application of TCM or the development of new drugs to treat DKD.

外文关键词：

herbal medicinecellular pyroptosisferroptosisdiabetic kidney diseaseoxidative stressinflammatory responserenal fibrosismechanism study

作者：

张雯年、李建省、王宝蕊、丁文君、康桂兰、贾路目草、陈银霞

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作者单位：

730030 兰州,甘肃中医药大学中西医结合学院

甘肃省中医院肾病科

甘肃省中医院儿科

关键词：

中药细胞焦亡铁死亡糖尿病肾病氧化应激炎症反应肾纤维化机制研究

基金：

国家自然科学基金国家中医药管理局青年岐黄学者支持项目甘肃省自然科学基金甘肃省自然科学基金甘肃省中医药科研项目(重点课题)甘肃省高等学校科研项目

项目编号：

82360884国中医药人教函[2020]218号20JR5RA16222JR5RA642GZKZ-2022-32013A-082

出版年：

2024

DOI：

10.3969/j.issn.1674-1749.2024.09.041

环球中医药

中华国际医学交流基金会

环球中医药

CSTPCD

影响因子：1.553

ISSN：1674-1749

年,卷(期)：2024.17(9)