[1]唐磊,徐国彤,张敬法.褪黑素治疗糖尿病视网膜病变的研究进展[J].眼科新进展,2021,41(7):684-687.[doi:10.13389/j.cnki.rao.2021.0142]
　TANG Lei,XU Guotong,ZHANG Jingfa.Progress of melatonin in the treatment of diabetic retinopathy[J].Recent Advances in Ophthalmology,2021,41(7):684-687.[doi:10.13389/j.cnki.rao.2021.0142]
点击复制

褪黑素治疗糖尿病视网膜病变的研究进展/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年7期
页码:
684-687
栏目:
文献综述
出版日期:
2021-07-05

文章信息/Info

Title:
Progress of melatonin in the treatment of diabetic retinopathy
作者:
唐磊; 徐国彤; 张敬法
200092　上海市，同济大学医学院，同济眼科研究所，同济大学医学院再生医学系及药理学系（唐磊，徐国彤）；200080　上海市，上海市第一人民医院眼科，国家眼部疾病临床医学研究中心，上海市眼底病重点实验室，上海眼视觉与光医学工程技术研究中心，上海市眼科疾病精准诊疗工程技术研究中心（张敬法）
Author(s):
TANG Lei1; XU Guotong1; ZHANG Jingfa2
1.Tongji Eye Institute, Department of Regenerative Medicine, Department of Pharmacology, Tongji University School of Medicine, Shanghai 200092, China
2.Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
关键词:
糖尿病视网膜病变; 炎症; 氧化应激; 褪黑素; 血-视网膜屏障
Keywords:
diabetic retinopathy;  inflammation;  oxidative stress; melatonin;  blood-retinal barrier
分类号:
R774
DOI:
10.13389/j.cnki.rao.2021.0142
文献标志码:
A
摘要:
糖尿病视网膜病变（DR）是糖尿病在眼部的并发症之一，是工作人群视力下降的主要原因。DR的发病机制复杂，炎症、氧化应激、内质网应激和自噬等诸多因素均参与了DR的病理生理过程，目前尚缺乏有效的治疗措施。褪黑素是人脑松果体的合成产物，可释放到脑脊液和血液中；褪黑素及其代谢物具有多种生理功能，对炎症和氧化应激均具有拮抗作用。在不同的病理生理条件下，褪黑素还具有调节自噬和凋亡的功能。本文就褪黑素在DR及其并发症中的应用及潜在治疗进行阐述，以期为治疗DR提供新的思路和治疗靶点。
Abstract:
Diabetic retinopathy (DR), one of the complications of diabetes mellitus in the eye, remains as the major cause of blindness in working-age population. The pathogenesis of DR is complex, and the inflammation, oxidative stress, endoplasmic reticulum stress, and autophagy, etc., are all involved in the pathophysiological process of DR, which lacks of effective treatments. Melatonin is a synthetic product of the pineal gland, released into both the cerebrospinal fluid and the blood. This indole and its metabolites have many physiological functions and play protective roles against inflammation and oxidative stress. In addition, melatonin can regulate autophagy and apoptosis under different pathophysiological conditions. In this study, the application and possible effects of melatonin in DR and its complications are discussed in order to provide new insights in treatment of DR and new therapeutic targets.

参考文献/References:

［1］　GUNDOGAN F C,YOLCU U,AKAY F,ILHAN A,OZGE G,UZUN S.Diabetic macular edema ［J］.Pak J Med Sci,2016,32(2):505-510.
［2］　DEHDASHTIAN E,MEHRZADI S,YOUSEFI B,HOSSEINZADEH A,REITER R J,SAFA M,et al.Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy,inflammation and oxidative stress ［J］.Life Sci,2018,193:20-33.
［3］　GIACCO F,BROWNLEE M.Oxidative stress and diabetic complications［J］.Circ Res,2010,107(9):1058-1070.
［4］　RBSAM A,PARIKH S,FORT P E.Role of inflammation in diabetic retinopathy ［J］.Int J Mol Sci,2018,19(4):942.
［5］　ADAMIEC-MROCZEK J,OFICJALSKA-MLYNCZAK J,MISIUK-HOJLO M.Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy:analysis of vitreous samples ［J］.Cytokine,2010,49(3):269-274.
［6］　JIANG T,CHANG Q,CAI J,FAN J,ZHANG X,XU G.Protective effects of melatonin on retinal inflammation and oxidative stress in experimental diabetic retinopathy ［J］.Oxid Med Cell Longev,2016,2016:3528274.
［7］　HOSSEINZADEH A,KAMRAVA S K,JOGHATAEI M T,DARABI R,SHAKERI-ZADEH A,SHAHRIARI M,et al.Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin ［J］.J Pineal Res,2016,61(4):411-425.
［8］　BEHRAM KANDEMIR Y,GUNTEKIN ,TOSUN V,KORUCUK N,BOZDEMIR M N.Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A) ［J］.Cell Mol Biol,2018,64(14):47-52.
［9］　REZVANFAR M R,HESHMATI G,CHEHREI A,HAGHVERDI F,RAFIEE F,REZVANFAR F.Effect of bedtime melatonin consumption on diabetes control and lipid profile ［J］.Int J Diab Dev Ctries,2017,37(1):74-77.
［10］　SUN H,WANG X,CHEN J,GUSDON A M,SONG K,LI L,et al.Melatonin treatment improves insulin resistance and pigmentation in obese patients with acanthosis nigricans ［J］.Int J Endocrinol,2018,2018:2304746.
［11］　DE OLIVEIRA A C,ANDREOTTI S,SERTIE R A L,CAMPANA A B,DE PROENA A R G,VASCONCELOS R P,et al.Combined treatment with melatonin and insulin improves glycemic control,white adipose tissue metabolism and reproductive axis of diabetic male rats ［J］.Life Sci,2018,199:158-166.
［12］　SARTORI C,DESSEN P,MATHIEU C,MONNEY A,BLOCH J,NICOD P,et al.Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice ［J］.Endocrinology,2009,150(12):5311-5317.
［13］　HUANG H,WANG Z,WENG S J,SUN X H,YANG X L.Neuromodulatory role of melatonin in retinal information processing ［J］.Prog Retin Eye Res,2013,32:64-87.
［14］　GOUDARZI M,KHODAYAR M J,HOSSEINI TABATABAEI S M T,GHAZNAVI H,FATEMI I,MEHRZADI S.Pre-treatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice ［J］.Clin Pharmacol,2017,31(6):625-635.
［15］　MAIOCCHI S L,MORRIS J C,REES M D,THOMAS S R.Regulation of the nitric oxide oxidase activity of myeloperoxidase by pharmacological agents ［J］.Biochem Pharmacol,2017,2017:90-115.
［16］　QIAO Y F,GUO W J,LI L,SHAO S,QIAO X,SHAO J J,et al.Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats ［J］.Mol Med Rep,2016,13(1):21-26.
［17］　DJORDJEVIC B,CVETKOVIC T,STOIMENOV T J,DESPOTOVIC M,ZIVANOVIC S,BASIC J,et al Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase,VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes ［J］.Eur J Pharmacol,2018,833:290-297.
［18］　FERNNDEZ A,ORDEZ R,REITER R J,GONZLEZ-GALLEGO J,MAURIZ J L.Melatonin and endoplasmic reticulum stress:relation to autophagy and apoptosis ［J］.J Pineal Res,2015,59(3):292-307.
［19］　GARCA J J,LPEZ-PINGARRN L,ALMEIDA-SOUZA P,TRES A,ESCUDERO P,GARCA-GIL F A,et al.Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes:a review ［J］.J Pineal Res,2014,56(3):225-237.
［20］　TRIVEDI P P,JENA G B,TIKOO K B,KUMAR V.Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis-associated colon carcinogenesis ［J］.Mol Carcinog,2016,55(3):255-267.
［21］　WANG H,HAN X,WITTCHEN E S,HARTNETT M E.TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation ［J］.Mol Vis,2016,22:116-128.
［22］　FENG D,WANG B,WANG L,ABRAHAM N,TAO K,HUANG L.Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings ［J］.J Pineal Res，2017,62(3):e12395.
［23］　PARK J H,SHIM H M,NA A Y,BAE K C,BAE J H,IM S S,et al.Melatonin prevents pancreatic β-cell loss due to glucotoxicity:the relationship between oxidative stress and endoplasmic reticulum stress ［J］.J Pineal Res,2014,56(2):143-153.
［24］　TUNGKUM W,JUMNONGPRAKHON P,TOCHARUS C,GOVITRAPONG P,TOCHARUS J.Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines ［J］.J Toxicol Sci,2017,42(1):63-71.
［25］　CHOI S I,KIM K S,OH J Y,JIN J Y,LEE G H,KIM E K.Melatonin induces autophagy via an mtor-dependent pathway and enhances clearance of mutant-TGFBIp ［J］.J Pineal Res,2013,54(4):361-372.
［26］　DE LUXAN-DELGADO B,POTES Y,RUBIO-GONZALEZ A,CABALLERO B,SOLANO J J,FERNANDEZ-FERNANDEZ M,et al.Melatonin reduces endoplasmic reticulum stress and autophagy in liver of leptin-deficient mice ［J］.J Pineal Res,2016,61(1):108-123.
［27］　RUI B B,CHEN H,JANG L,LI Z,YANG J M,XU W P,et al.Melatonin upregulates the activity of AMPK and attenuates lipid accumulation in alcohol-induced rats ［J］.Alcohol Alcohol,2016,51(1):11-19.
［28］　SHI H,ZHANG Z,WANG X,LI R,HOU W,BI W,et al.Inhibition of autophagy induces IL-1β release from ARPE-19 cells via ROS mediated NLRP3 inflammasome activation under high glucose stress ［J］.Biochem Biophys Res Commun,2015,463(4):1071-1076.
［29］　XIE M,HU A,LUO Y,SUN W,HU X,TANG S.Interleukin-4 and melatonin ameliorate high glucose and interleukin-1β stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells ［J］.Mol Vis,2014,20:921-928.
［30］　KOWLURU R A,MISHRA M.Oxidative stress,mitochondrial damage and diabetic retinopathy ［J］.Biochim Biophys Acta,2015,1852(11):2474-2483.
［31］　KOWLURU R A,SANTOS J M,ZHONG Q.Sirt1,a negative regulator of matrix metalloproteinase-9 in diabetic retinopathy ［J］.Invest Ophthalmol Vis Sci,2014,55(9):5653-5660.
［32］　HOU X,ROOKLIN D,FANG H,ZHANG Y.Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation ［J］.Sci Rep,2016,6(1):38186.

相似文献/References:

[1]杜玮 刘子扬 周艳艳 雒雷鸣.糖尿病视网膜病变与血清胆红素水平的关系[J].眼科新进展,2012,32(5):000.
[2]范松涛 卢建民.阿司匹林与糖尿病患者玻璃体出血以及玻璃体切割术疗效的相关性研究[J].眼科新进展,2012,32(11):000.
[3]李艳 李筱荣 袁佳琴 潘斌.糖尿病大鼠视网膜中VEGF、PEDF的表达与血-视网膜屏障损伤[J].眼科新进展,2013,33(1):000.
[4]李朝晖 崔治华 胡晓英 孟丽珠 张敬维.糖尿病视网膜病变激光面积与疗效的分析[J].眼科新进展,2013,33(2):000.
[5]冯冬梅 朱鸿 施彩虹.CXC趋化因子及其受体在糖尿病视网膜病变中的作用[J].眼科新进展,2013,33(6):000.
[6]牛淑玲.糖尿病视网膜病变患者HbAlc、FPG与血小板参数的变化及危险因素分析[J].眼科新进展,2013,33(7):000.
[7]毕春潮 王睿 王建洲 雷春灵 董晓娟 王小莉 薛晓辉.Ad-PEDF对糖尿病视网膜病变大鼠视网膜新生血管的抑制作用[J].眼科新进展,2013,33(8):000.
[8]杨萍 孙书明 李晓鹏.辛伐他汀对糖尿病视网膜病变和炎症因子的影响[J].眼科新进展,2013,33(8):000.
[9]罗文婷 孙大卫.血管黏附蛋白-1在眼科疾病中的研究进展[J].眼科新进展,2013,33(8):000.
[10]李小璐 马雅玲.糖尿病视网膜病变大鼠视网膜VEGF和PEDF的动态表达[J].眼科新进展,2013,33(9):000.
[11]兰文 陆燕 王春红 胡钦瑞 黄振平.糖尿病视网膜病变炎症的研究新进展[J].眼科新进展,2013,33(2):000.
[12]刘安琪,左中夫,吴传玲,等.Netrin-1对糖尿病视网膜病变大鼠的保护作用[J].眼科新进展,2020,40(1):011.[doi:10.13389/j.cnki.rao.2020.0003]
　LIU Anqi,ZUO Zhongfu,WU Chuanling,et al.Protective effect of Netrin-1 on rats with diabetic retinopathy[J].Recent Advances in Ophthalmology,2020,40(7):011.[doi:10.13389/j.cnki.rao.2020.0003]
[13]张凤俊,李晶明,刘秋平.糖尿病视网膜病变发病机制及潜在治疗研究进展[J].眼科新进展,2020,40(7):677.[doi:10.13389/j.cnki.rao.2020.0156]
　ZHANG Fengjun,LI Jingming,LIU Qiuping.Pathogenesis and potential treatment of diabetic retinopathy[J].Recent Advances in Ophthalmology,2020,40(7):677.[doi:10.13389/j.cnki.rao.2020.0156]
[14]孔慧,崔彦.CD40-ATP-P2X7/NLRP3炎症信号通路在糖尿病视网膜病变中的作用研究进展[J].眼科新进展,2021,41(9):879.[doi:10.13389/j.cnki.rao.2021.0184]
　KONG Hui,CUI Yan.Research progress of the CD40-ATP-P2X7/NLRP3 inflammatory pathway in diabetic retinopathy[J].Recent Advances in Ophthalmology,2021,41(7):879.[doi:10.13389/j.cnki.rao.2021.0184]
[15]司长峰,卜荔,徐楠,等.柴胡皂苷D对糖尿病视网膜病变大鼠的治疗作用[J].眼科新进展,2021,41(10):925.[doi:10.13389/j.cnki.rao.2021.0194]
　SI Changfeng,BU Li,XU Nan,et al.Therapeutical effect of Saikosaponin D on diabetic retinopathy of rats[J].Recent Advances in Ophthalmology,2021,41(7):925.[doi:10.13389/j.cnki.rao.2021.0194]
[16]孔慧,崔彦.糖尿病视网膜病变中视网膜内皮细胞功能障碍的研究进展[J].眼科新进展,2022,42(9):753.[doi:10.13389/j.cnki.rao.2022.0155]
　KONG Hui,CUI Yan.Research progress on retinal endothelial cell dysfunction in diabetic retinopathy[J].Recent Advances in Ophthalmology,2022,42(7):753.[doi:10.13389/j.cnki.rao.2022.0155]
[17]陈洪良,施健,娄雪莹,等.中性粒细胞胞外陷阱在糖尿病视网膜病变中作用的研究进展[J].眼科新进展,2023,43(9):747.[doi:10.13389/j.cnki.rao.2023.0150]
　CHEN Hongliang,SHI Jian,LOU Xueying,et al.Research progress on the effect of neutrophil extracellular traps in diabetic retinopathy[J].Recent Advances in Ophthalmology,2023,43(7):747.[doi:10.13389/j.cnki.rao.2023.0150]
[18]张敬法.炎症在糖尿病视网膜病变中的作用：发病机制及治疗策略[J].眼科新进展,2024,44(1):001.[doi:10.13389/j.cnki.rao.2024.0001]
　ZHANG Jingfa.Role of inflammation in diabetic retinopathy: pathogenesis and treatment strategies[J].Recent Advances in Ophthalmology,2024,44(7):001.[doi:10.13389/j.cnki.rao.2024.0001]
[19]刘磊,刘珊珊,胡菲菲,等.吴茱萸碱调节cAMP/PKA信号通路在糖尿病大鼠视网膜损伤中的作用[J].眼科新进展,2024,44(2):094.[doi:10.13389/j.cnki.rao.2024.0019]
　LIU Lei,LIU Shanshan,HU Feifei,et al.Impact of evodiamine on retinal injury in diabetic rats by regulating cyclic adenosine monophosphate/protein kinase A signaling pathway[J].Recent Advances in Ophthalmology,2024,44(7):094.[doi:10.13389/j.cnki.rao.2024.0019]

备注/Memo

备注/Memo:
国家自然科学基金面上项目（编号：81570852）；“重大新药创制”科技重大专项课题资助（编号：2019ZX09301113）
更新日期/Last Update: 2021-07-05