摘要
糖尿病肾脏疾病(DKD)是糖尿病(DM)常见的一种微血管并发症,也是造成终末期肾病(ESRD)的主要病因。肾间质纤维化(RIF)是DKD进展到ESRD的主要病理基础,显著增加了DKD患者的死亡率,给患者和社会带来了沉重的负担,是临床上亟待解决的问题。RIF的发病机制错综复杂,主要与细胞外基质(ECM)过度沉积、上皮细胞-间充质转化(EMT)、氧化应激、炎症反应、细胞自噬等相关。转化生长因子-β1/Smad(TGF-β1/Smad)、核转录因子-κB(NF-κB)、p38丝裂原活化蛋白激酶(p38 MAPK)、分泌型糖蛋白/β-连环蛋白(Wnt/β-catenin)、哺乳动物雷帕霉素靶蛋白(mTOR)、酪氨酸激酶/信号转导和转录激活因子(JAK/STAT)、神经源性位点缺口同源蛋白(Notch)、核因子E_(2)相关因子2(Nrf2)等多条信号通路介导了RIF的发生发展,是DKD治疗的新型靶点。由于其发病机制复杂,目前西医治疗以改善代谢的基础治疗为主,疗效欠佳,难以阻止DKD的病情进展,因此寻找新的治疗方法具有重要的临床意义。近年来,诸多研究证明中药可通过调控相关信号通路,从而减轻氧化应激、抑制炎症反应、调控细胞自噬等,达到治疗糖尿病肾脏疾病肾间质纤维化(DKD-RIF)的目的,具有多途径、多靶点、多环节、疗效显著的优势。但目前尚缺乏相关的总结性记载,基于此,笔者查阅了近年来国内外相关文献,综述了上述相关信号通路在DKD-RIF发生发展中的作用及中药调控相关信号通路治疗DKD-RIF的研究进展,以期为进一步的科学研究及临床实践提供新的思路与参考。
Diabetic kidney disease(DKD)is a common microvascular complication of diabetics mellitus(DM)and the leading cause of end-stage renal disease(ESRD).Renal interstitial fibrosis(RIF)is the primary pathological basis for DKD progression to ESRD,which significantly increases the mortality rate of DKD patients and burdens patients and society,and it is thus a clinical problem that needs to be solved urgently.The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix(ECM),epithelial-mesenchymal transition(EMT),oxidative stress,inflammation,and autophagy.Multiple signaling pathways such as transforming growth factor-β1/Smad(TGF-β1/Smad),nuclear transcription factor-κB(NF-κB),p38 mitogen-activated protein kinase(p38 MAPK),secretory glycoprotein/β-catenin(Wnt/β-catenin),mammalian target of rapamycin(mTOR),Janus kinase/signal transducer and activator of transcription(JAK/STAT),neurogenic site-gap homologous protein(Notch),and nuclear factor E_(2)-associated factor 2(Nrf2)mediate the development of RIF,which are currently novel targets for DKD therapy.Due to the complexity of its pathogenesis,the current Western medical treatment mainly focuses on essential treatment to improve metabolism,which has poor efficacy and is difficult to prevent the progression of DKD,so it is significant to find new treatment methods clinically.In recent years,many studies have proved that traditional Chinese medicine can alleviate oxidative stress,inhibit inflammatory response,and regulate cellular autophagy by modulating relevant signaling pathways,so as to treat RIF in DKD,which has the advantages of multipathway,multi-targeting,multi-linking,and significant therapeutic efficacy.However,there is still a lack of relevant summary.By reviewing the latest research reports in China and abroad,this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways,aiming to provide new ideas and references for further scientific research and clinical practice.
作者
朱玲玲
佘云
余江毅
严倩华
ZHU Lingling;SHE Yun;YU Jiangyi;YAN Qianhua(Nanjing University of Chinese Medicine,Nanjing 210023,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2024年第5期213-225,共13页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(82004286)
江苏省中医药管理局项目(ZT202206)
江苏省研究生实践创新计划项目(SJCX23_0873)。
