周桃桃,郭兆安

• 1:山东中医药大学第一临床医学院
• 2:山东中医药大学附属医院

摘要(Abstract)：

<正>糖尿病肾病(diabetic nephropathy, DN)是糖尿病的常见并发症,其发病增加了糖尿病患者的病死率。2019年糖尿病地图指出,全球约有4.63亿20～79岁成人患糖尿病,预计2030年将增至5.784亿。约15%～25%的1型糖尿病和30%～40%的2型糖尿病患者出现肾脏方面的损伤,并最终发展成终末期肾脏病(end-stage renal disease, ESRD),患病率达33.6%[1]。

关键词(KeyWords)： 糖尿病肾病;发病机制;炎症反应;内质网应激;自噬

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 周桃桃,郭兆安

参考文献(References)：

• [1] Weng J P,Bi Y.Epidemiological Status of Chronic Diabetic Complications in China[J].Chin Med J ( Engl),2015,128(24):3267-3269.
• [2] Huang Y,Liu Y,Li L,et al.Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy:implications for glomerular endothelial injury[J].BMC Nephrol,2014,15:142.
• [3] Fan W,Wen X,Zheng J,et al.LINC00162 participates in the pathogenesis of diabetic nephropathy via modulating the miR-383/HDAC9 signalling pathway[J].Artif Cells Nanomed Biotechnol,2020,48(1):1047-1054.
• [4] Yang L,Zhang Q,Wu Q,et al.Effect of TET2 on the pathogenesis of diabetic nephropathy through activation of transforming growth factor β1 expression via DNA demethylation[J].Life Sci,2018,207:127-137.
• [5] 陈林娜，张鹏，王汉民.DNA甲基化与糖尿病肾病的研究进展[J].医学研究杂志，2019,12(48):11-14.
• [6] Elneam A I,Mansour N M,Zaki N A,et al.Serum Interleukin-18 and Its Gene Haplotypes Profile as Predictors in Patients with Diabetic Nephropathy[J].Open Access Maced J Med Sci,2016,4(3):324-328.
• [7] 高红梅，唐亚，王俭勤.糖尿病肾病分子遗传学发病机制的研究进展[J].临床荟萃，2018,3(33):271-276.
• [8] Liu F,Fu Y,Wei C,et al.The expression of GPR109A,NF-κB and IL-1β in peripheral blood leukocytes from patients with type 2 diabetes[J].Ann Clin Lab Sci,2014,44(4):443-448.
• [9] Ojima A,Matsui T,Nishino Y,et al.Empagliflozin,an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis[J].Horm Metab Res,2015,47(9):686-692.
• [10] Wan Y G,Che X Y,Sun W,et al.Low-dose of multi-glycoside of Tripterygium wilfordii Hook.f.,a natural regulator of TGF-β1/Smad signaling activity improves adriamycin-induced glomerulosclerosis in vivo[J].J Ethnopharmaco,2014,151(3):1079-1089.
• [11] Sharma I,Tupe R S,Wallner A K,et al.Contribution of myo-inositol oxygenase in AGE:RAGE-mediated renal tubulointerstitial injury in the context of diabetic nephropathy[J].Am J Physiol Renal Physiol,2018,314(1):F107-F121.
• [12] 陈婷，陈雁虹，沈玮，等.野菊花提取物对糖尿病肾病大鼠的影响及作用机制[J].中国现代应用药学，2015,32(7):791-795.
• [13] Yan L J.Redox imbalance stress in diabetes mellitus:Role of the polyol pathway[J].Animal Model Exp Med,2018,1(1):7-13.
• [14] Wu J,Jin Z,Zheng H,et al.Sources and implications of NADH/NAD(+) redox imbalance in diabetes and its complications[J].Diabetes Metab Syndr Obes,2016,9:145-153.
• [15] Daroux M,Prévost G,Maillard-Lefebvre H,et al.Advanced glycation end-products:implications for diabetic and non-diabetic nephropathies[J].Diabetes Metab,2010,36(1):1-10.
• [16] Yerneni K K,Bai W,Khan B V,et al.Hyperglycemia-induced activation of nuclear transcription factor kappaB in vascular smooth muscle cells[J].Diabetes,1999,48(4):855-864.
• [17] Gilbert R E,Kim S A,Tuttle K R,et al.Effect of ruboxistaurin on urinary transforming growth factor-beta in patients with diabetic nephropathy and type 2 diabetes[J].Diabetes Care,2007,30(4):995-996.
• [18] 高星.彩色多普勒超声测量肾血流动力学参数对早期预测糖尿病肾病肾损害程度的诊断价值[J].实用医学影像杂志，2016,3(1):185-187.
• [19] 曹晔，杨丹，苏津，等.糖尿病肾病患者肾素-血管紧张素-醛固酮系统与血流动力学的关系[J].临床检验杂志，2012,12(22):1004-1005.
• [20] Macía-Heras M,Del Castillo-Rodriguez N,Navarro-González J.The renin-angiotensin-aldosterone system in renal and cardiovascular disease and the effects of its pharmacological blockade[J].J Diabetes Metab,2012,3:1-24.
• [21] 许雯雯，向少伟，任倩倩，等.糖尿病肾病的炎症机制与中医药治疗研究进展[J/OL].辽宁中医药大学学报，2020,22(11):141-145.
• [22] 王文文，韩文贝，万毅刚，等.糖尿病肾病NLRP3炎症小体活化的分子调控机制及中药的干预作用[J].中国中药杂志，2020,45(1):8-13.
• [23] Pálmai-Pallag,Timea,Bachrati,et al.Inflammation induced DNA damage and damage-induced inflammation:a vicious cycle[J].Microbes Infect,2014,16(10):822-832.
• [24] 陈烨，杨帆.炎症机制在糖尿病肾病中的作用[J].当代医学，2020,3(26):187-190.
• [25] Shen H,Ming Y,Xu C,et al.Deregulation of long noncoding RNA (TUG1) contributes to excessive podocytes apoptosis by activating endoplasmic reticulum stress in the development of diabetic nephropathy[J].J Cell Physiol,2019,PMID:30671964.
• [26] Cheng Y C,Chen C A,Chen H C.Endoplasmic reticulum stress-induced cell death in podocytes[J].Nephrology (Carlton),2017,22( Suppl 4):43-49.
• [27] Shao D,Ni J,Shen Y,et al.CHOP mediates XBPIS-induced renal mesangial cell necrosis following high glucose treatment[J].Eur J Pharmacol,2015,758:89-96.
• [28] Chiang C K,Wang C C,Lu T F,et al.Involvement of Endoplasmic Reticulum Stress,Autophagy,and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury[J].Sci Rep,2016,6:34167.
• [29] Pang X X,Bai Q,Wu F,et al.Urotensin II induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice[J].Kidney Blood Press Res,2016,41(4):434-449.
• [30] Susztak K,Raff A C,Schiffer M,et al.Glucose-induced re-active oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy[J].Diabetes,2006,55(1):225-233.
• [31] Jha J C,Banal C,Chow B S M,et al.Diabetes and kidney disease:role of oxidative stress[J].Antioxid Redox Signal,2016,25(12):657-684.
• [32] Sun L,Dutta R K,Xie P,et al.Myo-inositol oxygenase overexpression accentuates generation of reactive oxygen species and exacerbates cellular injury following high glucose ambience:A new mechanism relevant to the pathogenesis of diabetic nephropathy[J].J Biol Chem,2016,291(11):5688-5707.
• [33] Lu Q,Zhou Y,Hao M,et al.The mTOR promotes oxidative stress-induced apoptosis of mesangial cells in diabetic nephropathy[J].Mol Cell Endocrinol,2018,473:31-43.
• [34] Tagawa A,Yasuda M,Kume S,et al.Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy[J].Diabetes,2016,65(3):755-767.
• [35] Yamahara K,Yasuda M,Kume S,et al.The role of autophagy in the pathogenesis of diabetic nephropathy[J].J Diabetes Res,2013,2013:193757.
• [36] Fan Y,Yang Q,Yang Y,et al.Sirt6 Suppresses High Glucose-Induced Mitochondrial Dysfunction and Apoptosis in Podocytes through AMPK Activation[J].Int J Biol Sci,2019,15(3):701-713.
• [37] Huang C,Zhang Y,Kelly D J,et al.Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway[J].Sci Rep,2016,6:29196.
• [38] Musante L,Tataruch D E,Holthofer H.Use and isolation of urinary exosomes as biomarkers for diabetic nephropathy[J].Front Endocrinol (Lausanne),2014,5:149.
• [39] Sakurai A,Ono H,Ochi A,et al.Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy[J].PLoS One,2019,14(5):e0216788.
• [40] Delic D,Eisele C,Schmid R,et al.Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients[J].PLoS One,2016,11(3):e0150154.
• [41] Wu X M,Gao Y B,Cui F Q,et al.Exosomes from high glucose-treated glomerular endothelial cells activate mesangial cells to promote renal fibrosis[J].Biol Open,2016,5(4):484-491.
• [42] Wu X,Gao Y,Xu L,et al.Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes[J].Sci Rep,2017,7(1):9371.

文章评论(Comment)：