基于PERK-eIF2α-ATF4-CHOP通路探讨中医药干预糖尿病肾病的作用机制  

Mechanism of Action of Traditional Chinese Medicine in Intervention of Diabetic Nephropathy Based on PERK-eIF2α-ATF4-CHOP Pathway

作　　者：王茂泓[1] 郑航 李雪 张珍珍 WANG Mao-hong;ZHENG Hang;LI Xue;ZHANG Zhen-zhen(The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;Clinical Medical College,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学附属医院,南昌330006 [2]江西中医药大学临床医学院,南昌330004

出　　处：《科学技术与工程》2025年第8期3079-3088,共10页Science Technology and Engineering

基　　金：国家自然科学基金地区基金(82160879)。

摘　　要：糖尿病肾病发病机制复杂,最终可进展为终末期肾病,给患者带来沉重负担,目前的治疗手段疗效有限。蛋白激酶R样内质网激酶(protein kinase RNA-like endoplasmic reticulum kinase, PERK)-真核翻译起始因子2α激酶(eukaryotic initiation factor-2α, eIF2α)-转录激活因子4(activating transcription factor 4,ATF4)-C/EBP同源蛋白(C/EBP-homologous protein, CHOP)信号通路作为内质网应激的关键通路,其下游调控的细胞凋亡和自噬等病理过程与糖尿病肾病的进展关系密切。中医药通过益气养阴、健脾益肾、利水消肿、清热解毒、活血祛瘀等治法调控PERK-eIF2α-ATF4-CHOP通路,起到保护肾小球滤过屏障、减少毛细血管基底膜增厚、增加尿蛋白质重吸收、延缓肾间质纤维化的作用。阐释PERK-eIF2α-ATF4-CHOP信号通路在糖尿病肾病中的作用机制,归纳中医治法干预该通路的理论基础,总结中药有效成分干预该通路的作用机制的研究进展,旨在为中医药防治糖尿病肾病提供新的思路和方法。The pathogenesis of diabetic nephropathy is complex and can ultimately progress to end-stage renal disease,imposing a heavy burden on patients.Current treatment methods show limited efficacy.The protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic initiation factor-2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP)signaling pathway serves as a critical pathway in endoplasmic reticulum stress,with downstream regulation of pathological processes such as apoptosis and autophagy closely related to the progression of diabetic nephropathy.Traditional Chinese medicine regulates the PERK-eIF2α-ATF4-CHOP pathway through methods that tonify Qi and nourish Yin,strengthen the spleen and benefit the kidneys,promote diuresis and reduce edema,clear heat and detoxify,as well as invigorate blood and eliminate stasis.These interventions protect the glomerular filtration barrier,reduce capillary basement membrane thickening,enhance protein reabsorption in urine,and delay renal interstitial fibrosis.The mechanistic role of the PERK-eIF2α-ATF4-CHOP signaling pathway in diabetic nephropathy was elucidated,the theoretical basis for traditional Chinese medicine interventions in this pathway was summarized,and recent advances were reviewed in the mechanisms of action of effective components of traditional Chinese medicine targeting this pathway,aiming to provide new ideas and methods for the prevention and treatment of diabetic nephropathy through traditional Chinese medicine.

关 键 词：中医药 糖尿病肾病 内质网应激 蛋白激酶R样内质网激酶-C/EBP同源蛋白(PERK-CHOP)信号通路 

分 类 号：R259[医药卫生—中西医结合] R277.5[医药卫生—中医内科学]