糖尿病肾病病理机制及治疗措施的研究进展

doi:10.3969/j.issn.1674-490X.2020.01.001

摘要/Abstract

摘要： 糖尿病肾病是糖尿病中最常见的微血管并发症,是一种慢性进行性肾脏疾病。糖尿病肾病也是导致终末期肾病的主要原因之一。为了更好地保护和预防糖尿病肾病的进展,现总结了糖尿病肾病的相关病理机制以及靶向治疗措施,以降低心血管疾病的发病率和病死率,同时对于糖尿病肾病早期的干预和治疗至关重要。

关键词: 糖尿病肾病, 病理机制, 治疗措施

Abstract: Diabetic nephropathy(DN)is a severe microvascular complication of diabetes and is a chronic progressive kidney disease. Diabetic nephropathy is also a major cause of end-stage renal disease(ESRD). In order to better protect and prevent the progression of DN, this review summarizes the relevant pathological mechanisms of DN and targeted treatment measures to reduce the incidence and mortality of cardiovascular disease, and is essential for early intervention and treatment.

Key words: diabetic nephropathy, pathological mechanism, treatment measures

中图分类号:

R587.2

杨静,傅继华. 糖尿病肾病病理机制及治疗措施的研究进展[J]. 医学研究与教育, 2020, 37(1): 1-6.

参考文献

[1] WAKISAKA M, KAMOUCHI M, KITAZONO T. Lessons from the trials for the desirable effects of sodium glucose co-transporter 2 inhibitors on diabetic cardiovascular events and renal dysfunction[J]. Int J Mol Sci, 2019, 20(22): 5668. DOI: 10.3390/ijms20225668.
[2] GNUDI L, COWARD R J M, LONG D A. Diabetic nephropathy: perspective on novel molecular mechanisms[J]. Trends Endocrinol Metab, 2016, 27(11): 820-830. DOI: 10.1016/j.tem.2016.07.002.
[3] PIERRE-JEAN S, MANJULA D, WHEELOCK K M, et al. Urine metabolites are associated with glomerular lesions in type 2 diabetes[J]. Metabolomics, 2018, 14(6): 84. DOI: 10.1007/s11306-018-1380-6.
[4] BELLIN A R, ZHANG Y, THAI K, et al. Impaired SIRT1 activity leads to diminution in glomerular endowment without accelerating age-associated GFR decline[J]. Physiol Rep, 2019, 7(9): e14044. DOI: 10.14814/phy2.14044.
[5] SAGOO M K, GNUDI L. Diabetic nephropathy: is there a role for oxidative stress?[J]. Free Radic Biol Med, 2018, 116: 50-63. DOI: 10.1016/j.freeradbiomed.2017.12.040.
[6] TUTTLE K R. Back to the future: glomerular hyperfiltration and the diabetic kidney[J]. Diabetes, 2017, 66(1): 14-16. DOI: 10.2337/dbi16-0056.
[7] SANDHOLM N, VAN ZUYDAM N, AHLQVIST E, et al. The genetic landscape of renal complications in type 1 diabetes[J]. J Am Soc Nephrol, 2017, 28(2): 557-574. DOI: 10.1681/asn.2016020231.
[8] MILAS O, GADALEAN F, VLAD A, et al. Pro-inflammatory cytokines are associated with podocyte damage and proximal tubular dysfunction in the early stage of diabetic kidney disease in type 2 diabetes mellitus patients[J]. J Diabetes Complications, 2019: 107479. DOI: 10.1016/j.jdiacomp.2019.107479.
[9] SU H, WAN C, SONG A, et al. Oxidative stress and renal fibrosis: mechanisms and therapies[J]. Adv Exp Med Biol, 2019, 1165: 585-604. DOI: 10.1007/978-981-13-8871-2_29.
[10] TURKMEN K. Inflammation, oxidative stress, apoptosis, and autophagy in diabetes mellitus and diabetic kidney disease: the Four Horsemen of the Apocalypse[J]. Int Urol Nephrol, 2017, 49(5): 837-844. DOI: 10.1007/s11255-016-1488-4.
[11] ZHANG C X, LI Q, LAI S S, et al. Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin(STZ)-induced diabetic rats[J]. J Ethnopharmacol, 2017, 205: 207-216. DOI: 10.1016/j.jep.2017.05.009.
[12] NOGUERA C B, BAO S, PETERSEN K J, et al. Using deep learning for a diffusion-based segmentation of the dentate nucleus and its benefits over atlas-based methods[J]. J Med Imaging, 2019, 6(4): 044007. DOI: 10.1117/1.JMI.6.4.044007.
[13] QIAO Y C, CHEN Y L, PAN Y H, et al. Changes of transforming growth factor beta 1 in patients with type 2 diabetes and diabetic nephropathy[J]. Medicine, 2017, 96(15): e6583. DOI: 10.1097/md.0000000000006583.
[14] HOU B Y, QIANG G F, ZHAO Y R, et al. Salvianolic acid A protects against diabetic nephropathy through ameliorating glomerular endothelial dysfunction via inhibiting AGE-RAGE signaling[J]. Cell Physiol Biochem, 2017, 44(6): 2378-2394. DOI: 10.1159/000486154.
[15] LIU Q Y, DUAN Q, FU X H, et al. Value of elastography point quantification in improving the diagnostic accuracy of early diabetic kidney disease[J]. World J Clin Cases, 2019, 7(23): 3945-3956. DOI: 10.12998/wjcc.v7.i23.3945.
[16] WANG Z J, HAN Z J, TAO J, et al. Role of endothelial-to-mesenchymal transition induced by TGF-β1 in transplant kidney interstitial fibrosis[J]. J Cell Mol Med, 2017, 21(10): 2359-2369. DOI: 10.1111/jcmm.13157.
[17] CHEN Z Y, YUAN Y Y, ZOU X R, et al. Radix puerariae and fructus crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K[J]. BMC Complement Altern Med, 2017, 17: 454. DOI: 10.1186/s12906-017-1945-3.
[18] DEWANJEE S, BHATTACHARJEE N. MicroRNA: a new generation therapeutic target in diabetic nephropathy[J]. Biochem Pharmacol, 2018, 155: 32-47. DOI: 10.1016/j.bcp.2018.06.017.
[19] RAMOS A M, FERNANDEZFERNANDEZ B, PEREZGOMEZ M V, et al. Design and optimization strategies for the development of new drugs that treat chronic kidney disease[J]. Expert Opin Drug Discov, 2019, 15(1): 101-115. DOI: 10.1080/17460441.2020.1690450.
[20] MOSENZON O, LEIBOWITZ G, BHATT D L, et al. Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial[J]. Dia Care, 2017, 40(1): 69-76. DOI: 10.2337/dc16-0621.
[21] MIZUIRI S. ACE and ACE2 in kidney disease[J]. World J Nephrol, 2015, 4(1): 74. DOI: 10.5527/wjn.v4.i1.74.
[22] LIU C X, HU Q, WANG Y, et al. Angiotensin-converting enzyme(ACE)2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy: A comparison with ACE inhibition[J]. Mol Med, 2011, 17(1/2): 59-69. DOI: 10.2119/molmed.2010.00111.
[23] WANG L F, LIN W Q, CHEN J H. Krüppel-like factor 15: a potential therapeutic target for kidney disease[J]. Int J Biol Sci, 2019, 15(9): 1955-1961. DOI: 10.7150/ijbs.34838.
[24] JAMES M T, MANNS B J. Neprilysin inhibition and effects on kidney function and surrogates of cardiovascular risk in chronic kidney disease[J]. Circulation, 2018, 138(15): 1515-1518. DOI:10.1161/CIRCULATIONAHA.118.036523.
[25] BENIGNI A, ZOJA C, ZATELLI C, et al. Vasopeptidase inhibitor restores the balance of vasoactive hormones in progressive nephropathy[J]. Kidney Int, 2004, 66(5): 1959-1965. DOI: 10.1111/j.1523-1755.2004.00982.x.
[26] GUZZI F, CIRILLO L, ROPERTO R M, et al. Molecular mechanisms of the acute kidney injury to chronic kidney disease transition: An Updated View[J]. Int J Mol Sci, 2019, 20(19): 4941. DOI: 10.3390/ijms20194941.
[27] PANCHAPAKESAN U, PEGG K, GROSS S, et al. Effects of SGLT2 inhibition in human kidney proximal tubular cells: renoprotection in diabetic nephropathy?[J]. Plos One, 2013, 8(2): e54442. DOI: 10.1371/journal.pone.0054442.
[28] KOJIMA N, WILLIAMS J M, TAKAHASHI T, et al. Effects of a new SGLT2 inhibitor, luseogliflozin, on diabetic nephropathy in T2DM rats[J]. J Pharmacol Exp Ther, 2013, 345(3): 464-472. DOI: 10.1124/jpet.113.203869.
[29] SUN A L, DENG J T, GUAN G J, et al. Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease[J]. Diabetes Vasc Dis Res, 2012, 9(4): 301-308. DOI: 10.1177/1479164111434318.
[30] ISAKA Y. Targeting TGF-β signaling in kidney fibrosis[J]. Int J Mol Sci, 2018, 19(9): 2532. DOI: 10.3390/ijms19092532.
[31] KIM Y, KIM S, KIM K, et al. The role of inflammasome-dependent and inflammasome-independent NLRP3 in the kidney[J]. Cells, 2019, 8(11):1389. DOI: 10.3390/cells8111389.
[32] MANNUCCI E, PALA L, CIANI S, et al. Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus[J]. Diabetologia, 2005, 48(6): 1168-1172. DOI: 10.1007/s00125-005-1749-8.
[33] ELSEWEIDY M M, ELSWEFY S E, YOUNIS N N, et al. Pyridoxamine, an inhibitor of protein glycation, in relation to microalbuminuria and proinflammatory cytokines in experimental diabetic nephropathy[J]. Exp Biol Med, 2013, 238(8): 881-888. DOI: 10.1177/1535370213494644.
[34] TANG Y T, ZHANG F F, HUANG L, et al. The protective mechanism of fluorofenidone in renal interstitial inflammation and fibrosis[J]. Am J Med Sci, 2015, 350(3): 195-203. DOI: 10.1097/maj.0000000000000501.
[35] HANSSEN N M, RUSSELL N, COOPER M E. Recent advances in glucose-lowering treatment to reduce diabetic kidney disease[J]. Expert Opin Pharmacother, 2015, 16(9): 1325-1333. DOI: 10.1517/14656566.2015.1041502.
[36] LIU Y N, ZHOU J W, LI T T, et al. Sulodexide protects renal tubular epithelial cells from oxidative stress-induced injury via upregulating klotho expression at an early stage of diabetic kidney disease[J]. J Diabetes Res, 2017, 2017: 1-10. DOI: 10.1155/2017/4989847.