摘要：泌尿系结石是一种泌尿系统的常见性、易复发性疾病，其病因及发病机制尚不明确。肾脏是对氧化还原失 衡特别敏感的器官，过量生成的活性氧簇和氧化应激参与了肾小管上皮细胞损伤、炎症和肾结石的病理形成。肾 脏 Randall斑的存在证实了氧化应激可诱导肾脏损伤、结石生成。流行病学研究发现，肾结石与全身代谢性疾病 密切相关，故可将肾结石视为一种慢性代谢性疾病，而氧化应激可能是它们共同的病理生理学基础。本文旨在阐 释氧化应激在肾结石形成中的作用机制，总结归纳氧化应激作为肾结石治疗靶点的潜力，为泌尿系结石的防治提 供新思路。

暂无相关信息！

[1] ZENG G, MAI Z, XIA S, et al. Prevalence of kidney stones in China: an ultrasonography based cross: ectional study [J]. BJU Int, 2017,120(1):109-116

[2] MOE OW. Kidney stones: pathophysiology and medical management [J]. Lancet, 2006,367(9507):333-344

[3] KHAN SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations [J]. J Urol, 2013,189(3):803-811

[4] SIES H. Oxidative stress: a concept in redox biology and medicine [J]. Redox Biol, 2015,4:180-183

[5] OZBEK E. Induction of oxidative stress in kidney [J]. Int J Nephrol, 2012,2012:465897

[6] GORIN Y. The Kidney: An organ in the front line of oxidative stress- associated pathologies [J]. Antioxid Redox Signal, 2016,25(12):639-641

[7] JHA JC, BANAL C, CHOW BS, et al. Diabetes and kidney disease: role of oxidative stress [J]. Antioxid Redox Signal, 2016,25(12):657-684

[8] KALYANARAMAN B. Teaching the basics of redox biology to medical and graduate students: Oxidants, antioxidants and disease mechanisms [J]. Redox Biol, 2013,1: 244-257

[9] RANDALL A. The origin and growth of renal calculi [J]. Ann Surg, 1937,105(6):1009-1027

[10] BOROFSKY MS, DAUW CA, COHEN A, et al. Integration and utilization of modern technologies in nephrolithiasis research [J]. Nat Rev Urol, 2016,13(9):549-557

[11] EVAN AP, LINGEMAN JE, COE FL, et al. Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle [J]. J Clin Invest, 2003, 111(5):607-616

[12] EVAN AP, LINGEMAN JE, COE FL, et al. Role of interstitial apatite plaque in the pathogenesis of the common calcium cxalate Stone [J]. Semin Nephrol, 2008,28(2): 111-119

[13] LIESKE JC, DEGANELLO S. Nucleation, adhesion, and internalization of calcium- containing urinary crystals by renal cells [J]. J Am Soc Nephrol, 1999,10 Suppl 14(11): S422-S429

[14] EVAN AP, WORCESTER EM, COE FL, et al. Mechanisms of human kidney stone formation [J]. Urolithiasis, 2015,43(1):19-32

[15] TAYLOR EN, STAMPFER MJ, CURHAN GC. Obesity, weight gain, and the risk of kidney stones [J]. JAMA, 2005,293(4):455-462

[16] CAPPUCCIO FP, STRAZZULLO P, MANCINI M. Kidney stones and hypertension: population based study of an independent clinical association [J]. BMJ, 1990,300 (6734):1234-1236

[17] WEINBERG AE, PATEL CJ, CHERTOW GM, et al. Diabetic severity and risk of kidney stone disease [J]. Eur Urol, 2014,65(1):242-247

[18] TORRICELLI FC, DE SK, GEBRESELASSIE S, et al. Dyslipidemia and kidney stone risk [J]. J Urol, 2014, 191(3):667-672

[19] JEONG IG, KANG T, BANG JK, et al. Association between metabolic syndrome and the presence of kidney stones in a screened population [J]. Am J Kidney Dis, 2011,58(3):383-388

[20] FERRARO PM, TAYLOR EN, EISNER BH, et al. History of kidney stones and risk of coronary heart disease [J]. JAMA, 2013,310(4):408-415

[21] SAUCIER NA, SINHA MK, LIANG KV, et al. Risk factors for CKD in persons with kidney stones:acase- control study in olmsted county, Minnesota [J]. Am J Kidney Dis, 2010,55(1):61-68

[22] SHARMA K. Obesity and Diabetic Kidney Disease: Role of Oxidant Stress and Redox Balance [J]. Antioxid Redox Signal, 2016,25(4):208-216

[23] KHAN SR. Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome? [J]. Urol Res, 2012,40(2): 95-112

[24] ZUO L, TOZAWA K, OKADA A, et al. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment [J]. J Urol, 2014,191 (6):1906-1912

[25] ICHIKAWA J, OKADA A, TAGUCHI K, et al. Increased crystal- cell interaction in vitro under co- culture ofrenal tubular cells and adipocytes by in vitro co- culture paracrine systems simulating metabolic syndrome[J]. Urolithiasis, 2014,42(1):17-28

[26] SáENZ- MEDINA J, JORGE E, CORBACHO C, et al. Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis [J]. Urolithiasis, 2018,46(2):179-186

[27] AMIN R, ASPLIN J, JUNG D, et al. Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity- associated hyperoxaluria [J]. Kidney Int, 2018,93(5):1098-1107

[28] SASAKI Y, KOHJIMOTO Y, IBA A, et al. Weight loss intervention reduces the risk of kidney stone formation in a rat model of metabolic syndrome [J]. Int J Urol, 2015,22(4):404-409

[29] VEENA CK, JOSEPHINE A, PREETHA SP, et al. Mitochondrial dysfunction in an animal model of hyperoxaluria:a prophylactic approach with fucoidan [J]. Eur J Pharmacol, 2008,28(579):330-336

[30] KHAN A, BYER K, KHAN SR. Exposure of MadinDarby canine kidney (MDCK) cells to oxalate and calcium oxalate crystals activates nicotinamide adenine dinucleotide phosphate (NADPH)- oxidase [J]. Urology, 2014,83(2):510. e1-510.e7

[31] ZUO J, KHAN A, GLENTON PA, et al. Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy- L- proline- induced hyperoxaluria in the male Sprague- Dawley rats [J]. Nephrol Dial Transplant, 2011, 26(6):1785-1796

[32] YOSHIOKA I, TSUJIHATA M, AKANAE W, et al. Angiotensin type- 1 receptor blocker candesartan inhibits calcium oxalate crystal deposition in ethylene glycol- treated rat kidneys [J]. Urology, 2011,77(4):9-14

[33] QIN B, WANG Q, LU Y, et al. Losartan Ameliorates calcium oxalate- induced elevation of stone- related proteins in renal tubular cells by Inhibiting NADPH oxidase and oxidative stress [J]. Oxid Med Cell Longev, 2018, 2018: 1271864

[34] TSUJIHATA M, YOSHIOKA I, TSUJIMURA A, et al. Why does atorvastatin inhibit renal crystal retention? [J]. Urol Res, 2011,39(5):379-383

[35] JOSHI S, PECK AB, KHAN SR. NADPH oxidase as a therapeutic target for oxalate induced injury in kidneys [J]. Oxid Med Cell Longev, 2013,2013(5):462361

[36] CHUNG J, GRANJA I, TAYLOR MG, et al. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition [J]. Nature, 2016,536(7617):446-450. 

周建甫,王树声,向松涛. 氧化应激在肾结石防治中的研究进展[J]. 泌尿外科杂志（电子版）,2021,13(3):90-93. DOI:10.3969/j.issn.1674-7410.2021.03.022.

暂无相关信息！

泌尿系结石指人体尿液中固体成分析出后在泌 尿系统各部位形成的一种病理性生物矿化疾病，原 发部位主要在肾脏。近年来我国泌尿系结石的发病 率不断升高，最近的一项横断面流行病学调查显 示，我国肾结石总患病率为 6.5%，其中南方地区高 达 10%[1] 。泌尿系结石复发率高，5 年复发率为 50% 左右，10 年复发率高达 75%，给患者和社会带来了 沉重的负担[2] 。目前肾结石的病因和形成机制尚未明 确，一般认为其形成过程主要包括尿液过饱和、异 质成核、晶体生长与聚集、晶体黏附并沉积于肾。 近年来大量的研究表明，草酸和晶体诱导的肾小管 上皮细胞损伤、炎性反应与肾结石的病理形成密切 相关，活性氧 （reactive oxygen species，ROS） 诱导的氧化应激 （oxidative stress，OS） 在其中发挥关键调控作用[3] 。为此，本文将阐释 OS 在肾结石形 成中的作用机制，总结归纳 OS作为肾结石治疗靶点 的潜力，为泌尿系结石的防治提供新思路。

1 肾脏的氧化/抗氧化病理、生理学基础

2 Randall 斑：OS 诱导肾损伤的临床证据

3 OS 是全身代谢性疾病与肾结石的共同通路

4 还原型辅酶Ⅱ （nicotinamide adenine dinucleotide phosphate，NADPH） 氧化酶：一个新兴的肾 结石治疗靶点

5 小结

5 小结 

泌尿系结石是一种多因素、多步骤的代谢相关 性疾病，OX介导的肾小管上皮细胞损伤在结石形成 中发挥关键作用，NADPH 氧化酶介导生成 ROS， 是肾结石一个的新兴治疗靶点，靶向 OX是泌尿系结 石病因学预防的重要策略[36] 。

暂无相关信息！

暂无相关信息！