[1]孙洪岩,滕岩,杨明明.自噬的分子机制及其在糖尿病视网膜病变中的作用[J].眼科新进展,2019,39(10):984-987.[doi:10.13389/j.cnki.rao.2019.0225]
　SUN Hong-Yan,TENG Yan,YANG Ming-Ming.Molecular mechanism of autophagy and its role in diabetic retinopathy[J].Recent Advances in Ophthalmology,2019,39(10):984-987.[doi:10.13389/j.cnki.rao.2019.0225]
点击复制

自噬的分子机制及其在糖尿病视网膜病变中的作用/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年10期
页码:
984-987
栏目:
文献综述
出版日期:
2019-10-05

文章信息/Info

Title:
Molecular mechanism of autophagy and its role in diabetic retinopathy
作者:
孙洪岩; 滕岩; 杨明明
150001　黑龙江省哈尔滨市，哈尔滨医科大学附属第一医院眼科医院
Author(s):
SUN Hong-Yan; TENG Yan; YANG Ming-Ming
Department of Ophthalmology，The First Affiliated Hospital of Harbin Medical University，Harbin 150001，Heilongjiang Province,China
关键词:
糖尿病视网膜病变; 自噬; 分子机制; 氧化应激
Keywords:
diabetic retinopathy;  autophagy; molecular mechanism; oxidative stress
分类号:
R774.1
DOI:
10.13389/j.cnki.rao.2019.0225
文献标志码:
A
摘要:
糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病微血管并发症之一，具有特征性的眼底表现，是临床上导致糖尿病患者失明的重要原因。近年来DR的发病率显著增长，严重威胁到糖尿病患者的身心健康，已成为关乎民众健康乃至国计民生的社会问题。DR发病机制复杂，多种因素如氧化应激、缺氧、炎症反应、内质网应激、多元醇途径等，均被证实与DR的发病密切相关。近年研究发现，自噬作为机体一种重要的防御机制，参与了DR的发生与发展，其病理过程涉及多种信号转导通路，与氧化应激、缺氧及新生血管形成尤为相关。因此，自噬与DR的关系成为临床研究的热点。
Abstract:
Diabetic retinopathy (DR) is a microvascular complication of diabetes with a characteristic fundus manifestation，which has been a leading cause of blindness across the globe.In recent years,DR has been reaching an alarming proportion significantly,which has become a greater threat to the physical and mental health of diabetic patients.It has become a social problem related to the health of the people and even the national economy and the people’s livelihood.DR has a complex multifactorial pathogenesis and the exact mechanism has not been well elucidated.Many factors,such as oxidative stress,hypoxia,inflammation,endoplasmic reticulum stress and polyol pathway,have been identified to be involved in the pathogenesis of DR.Recent studies have found that autophagy,as an important innate defense mechanism,is involved in the development of DR.Its pathological process involves a variety of signal transduction pathways,in particularly related to oxidative stress,hypoxia and angiogenesis.Therefore,the relationship between autophagy and diabetic retinopathy has become a hot topic in clinical research.

参考文献/References:

［1］　JI L N，LU J M，GUO X H，YANG W Y，WENG J P，JIA W P，et al.Status of blood glucose control and treatment of type 2 diabetes in China［J］.Chin J Diabetes Mellitus，2012，4（7）：397-401.
级立农，陆菊明，郭晓慧，杨文英，翁建平，贾伟平，等.中国2型糖尿病药物治疗现状与血糖控制的调查研究［J］.中华糖尿病杂志，2012，4（7）：397-401.
［2］　INGELFINGER J R，JARCHO J A.Increase in the incidence of diabetes and its implications［J］.N Engl J Med，2017，376（15）：1473-1474.
［3］　FRANK R N.Diabetic retinopathy and systemic factors［J］.Middle East Afr J Ophthalmol，2015，22（2）：151-156.
［4］　WAN T T，LI X F，SUN Y M，LI Y B，SU Y.Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy［J］.Biomed Pharmacother，2015，74：145-147.
［5］　ROSA M D，DISTEFANO G，GAGLIANO C，RUSCIANO D，MALA-GUARNERA L.Autophagy in diabetic retinopathy［J］.Curr Neuropharmacol，2016，14（8）：810-825.
［6］　WATADA H，FUJITANI Y.Minireview：Autophagy in pancreatic beta-cells and its implication in diabetes［J］.Mol Endocrinol，2015，29（3）：338-348.
［7］　CAO J，YING M，XIE N，LIN G，DONG R，ZHANG J，et al.The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr：autophagy or apoptosis?［J］.Antioxid Redox Signal，2014，21（10）：1443-1459.
［8］　WU W H，ZHANG M P，ZHANG F，LIU F，HU Z X，HU Q D，et al.The role of programmed cell death in streptozotocin-induced early diabetic nephropathy［J］.J Endocrinol Invest，2011，34（9）：e296-301.
［9］　PENG K Y，HORNG L Y，SUNG H C，HUANG H C，WU R T.Hepatocyte growth factor has a role in the amelioration of diabetic vascular complications via autophagic clearance of advanced glycation end products：Dispo85E，an HGF inducer，as a potential botanical drug［J］.Metabolism，2011，60（6）：888-892.
［10］　MIZUSHIMA N，KOMATSU M.Autophagy：renovation of cells and tissues［J］.Cell，2011，147（4）：728-741.
［11］　SAHU R，KAUSHINK S，CLEMENT C C，CANNIZZO E S，SCHARF B，FOLLENZI A，et al.Microautophagy of cytosolic proteins by late endosomes［J］.Dev Cell，2011，20（1）：131-139.
［12］　ORENSTEIN S J，CUERVO A M.Chaperone-mediated autophagy：molecular mechanisms and physiological relevance［J］.Semin Cell Dev Biol，2010，21（7）：719-726.
［13］　LI M，JIANG X，LIU D，NA Y，GAO G F，XI Z.Autophagy protects LNCaP cells under androgen deprivation conditions［J］.Autophagy，2008，4（1）：54-60.
［14］　HE C，KLIONSKY D J.Regulation mechanisms and signaling pathways of autophagy［J］.Annu Rev Genet，2009，43：67-93.
［15］　KIM M S，SONG S Y，LEE J Y，YOO N J，LEE S H.Expressional and mutational analyses of ATG5 gene in prostate cancers［J］.APMIS，2011，119（11）：802-807.
［16］　CHOI S E，LEE S M，LEE Y J，LI L J，LEE S J，LEE J H，et al.Protective role of autophagy in palmitate-induced INS-1 beta-cell death［J］.Endocrinology，2009，150（1）：126-134.
［17］　BALMER D，EMERY M，ANDREUX P，AUWERX J，GINET V，PUYAL J，et al.Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells［J］.PLoS One，2013，8（9）：e74162.
［18］　GENG Q R，XU D Z，HE L J，LU J B，ZHOU Z W，ZHAN Y Q，et al.Beclin-1 expression is a significant predictor of survival in patients with lymph node-positive gastric cancer［J］.PLoS One，2012，7（9）：e45968.
［19］　LOPES DE FARIA J M，DUARTE D A，MONTEMURRO C，PAPADIMITRIOU A，CONSONNI S R，LOPES DE FARIA J B.Defective autophagy in diabetic retinopathy［J］.Invest Ophthalmol Vis Sci，2016，57（10）：4356-4366.
［20］　DING K，WU Z，WANG N，WANG X，WANG Y，QIAN P，et al.MiR-26a performs converse roles in proliferation and metastasis of different gastric cancer cells via regulating of PTEN expression［J］.Pathol Res Pract，2017，213（5）：467-475.
［21］　KANAMORI Y，KIGAWA J，ITAMOCHI H，SULTANA H，SUZUKI M，OHWADA M，et al.PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy［J］.Int J Cancer，2002，100（6）：686-689.
［22］　SUN J，LI Z P，ZHANG R Q，ZHANG H M.Repression of miR-217 protects against high glucose-induced podocyte injury and insulin resistance by restoring PTEN-mediated autophagy pathway［J］.Biochem Biophys Res Commun，2017，483（1）：318-324.
［23］　PRUSZKO M，MILANO E，ZYLICZ A，ZYLICZ M，BLANDINO G，FONTEMAGGI G.Zebrafish as experimental model to establish the contribution of mutant p53 and ID4 to breast cancer angiogenesis in vivo［J］.J Thorac Dis，2018，10（3）：E231-E233.
［24］　SAM M R，TAVAKOIL-MEHR M，SAFARALIZADEH R.Omega-3 fatty acid DHA modulates p53，survivin，and microRNA-16-1 expression in KRAS-mutant colorectal cancer stem-like cells［J］.Genes Nutr，2018，13：8.
［25］　LIU Q，WANG J J，PAN Y C，MENG L F，ZHAN X，ZHNEG Q F.Expression of autophagy-related genes Beclin1 and MAPLC3 in non-small cell lung cancer［J］.Ai Zheng，2008，27（1）：25-29.
［26］　LIU Q，WEI F，XU X.Expression and siginificant of LC3 in the retina of early stage diabetic rats［J］.Chin J Ophthalmol Otorhinolaryngol，2017,17（1）：10-15.
刘青，韦芳，许讯.LC3在早期糖尿病大鼠视网膜的表达和意义［J］.中国眼耳鼻喉科杂志,2017,17（1）：10-15.
［27］　HOUSTIS N，ROSEN E D，LANDER E S.Reactive oxygen species have a causal role in multiple forms of insulin resistance［J］.Nature，2006，440（7086）：944-948.
［28］　DIN F V，VALANCIUTE A，HOUDE V P，ZIBROVA D，GREEN K A，SAKAMOTO K，et al.Aspirin inhibits mTOR signaling，activates AMP-activated protein kinase，and induces autophagy in colorectal cancer cells［J］.Gastroenterology，2012，142（7）：1503-1515.
［29］　FILOMENI G，DE Z D，CECCONI F.Oxidative stress and autophagy：the clash between damage and metabolic needs［J］.Cell Death Differ，2015，22（3）：377-388.
［30］　WANG K K，XIAO H，CHEN A L，ZOU J，YI Y X，CHEN G W，et al.Role of autophagy in vascular endothelial growth factor induced endothelial cell formation［J］.Chin J Pathophysiol，2012，28（11）：2040.
王慷慨，肖卉，陈岸兰，邹江，易宇欣，陈广文，等.自噬在血管内皮生长因子诱导的内皮细胞管型形成中的作用［J］.中国病理生理杂志，2012，28（11）：2040.
［31］　DU J H，LIU J L，MA L，LI R，ZHANG Z，LI J Q，et al.Autophagy inhibitor 3-methylademine inhibits angiogenesis of RF/6A cells caltured in high glucose［J］.J Clin Ophthalmol，2015，23：456-460.
杜军辉，刘佳丽，马乐，李蓉，张中，李俊琪，等.自噬抑制剂3-MA抑制高糖条件下猴脉络膜视网膜血管内皮细胞血管形成［J］.临床眼科杂志2015，23：456-460.
［32］　LAI H H，LI J N，WANG M Y，HUANG H Y，CROCE C M，SUN H L，et al.HIF-1alpha promotes autophagic proteolysis of Dicer and enhances tumor metastasis［J］.J Clin Invest，2018，128（2）：625-643.
［33］　TREINS C，GIORGETTI-PERALDI S，MURDACA J，MONTH-OUEL-KARTMANN M N，VAN OBBERGHEN E.Regulation of hypoxia-inducible factor （HIF）-1 activity and expression of HIF hydroxylases in response to insulin-like growth factor I［J］.Mol Endocrinol，2005，19（5）：1304-1317.
［34］　LIU L，NING X，HAN S，ZHANG H，SUN L，SHI Y，et al.Hypoxia induced HIF-1 accumulation and VEGF expression in gastric epithelial mucosa cell：involvement of ERK1/2 and PI3K/Akt［J］.Mol Biol （Mosk），2008，42（3）：459-469.
［35］　SKINNER H D，ZHENG J Z，FANG J，AGANI F，JIANG B H.Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1alpha，HDM2，and p70S6K1 in response to phosphatidylinositol 3-kinase/AKT signaling［J］.J Biol Chem，2004，279（44）：45643-45651.
［36］　LIANG J，SHAO S H，XU Z X，HENNESSY B，DING Z，LARREA M，et al.The energy sensing LKB1-AMPK pathway regulates p27（kip1） phosphorylation mediating the decision to enter autophagy or apoptosis［J］.Nat Cell Biol，2007，9（2）：218-224.
［37］　KUZUYA M，RAMOS M A，KANDA S，KOIKE T，ASAI T，MAEDA K，et al.VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor［J］.Arterioscler Thromb Vasc Biol，2001，21（5）：765-770.
［38］　OUIMET M，MARCEL Y L.Regulation of lipid droplet cholesterol efflux from macrophage foam cells［J］.Arterioscler Thromb Vasc Biol，2012，32（3）：575-581.
［39］　GHARBI C，GUEUTIN V，IZZEDINE H.Oedema，solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors （mTOR-I/PSIs）［J］.Clin Kidney J，2014，7（2）：115-120.
［40］　WON S J，YEN C H，LIU H S，WU S Y，LAN S H，JIANG-SHIEH Y F，et al.Justicidin A-induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway［J］.J Cell Physiol，2015，230（4）：930-946.
［41］　SHI W，XU D，GU J，XUE C，YANG B，FU L，et al.Saikosaponin-d inhibits proliferation by up-regulating autophagy via the CaMKKbeta-AMPK-mTOR pathway in ADPKD cells［J］.Mol Cell Biochem，2018,449(1-2):219-226.
［42］　OZDEMIR G，KILINC M，ERGUN Y，SAHIN E.Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy［J］.Can J Ophthalmol，2014，49（5）：443-449.

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]李蓉,姚杨,杜军辉,等.自噬在高糖条件下视网膜色素上皮细胞表达血管内皮生长因子促进RF/6A细胞血管生成中的作用[J].眼科新进展,2019,39(8):714.[doi:10.13389/j.cnki.rao.2019.0163]
　LI Rong,YAO Yang,DU Jun-Hui,et al.Autophagy promotes angiogenesis of RF/6A cells following upregulating the expression of vascular endothelial growth factor in retinal pigment epithelial cells under high glucose conditions[J].Recent Advances in Ophthalmology,2019,39(10):714.[doi:10.13389/j.cnki.rao.2019.0163]
[12]冯路迦,张学东.自噬与HMGB1在糖尿病视网膜微血管病变和神经退行性变中的研究进展[J].眼科新进展,2020,40(4):392.[doi:10.13389/j.cnki.rao.2020.0091]
　FENG Lujia,ZHANG Xuedong.Research advances on autophagy and HMGB1 in retinal microangiopathy and neurodegeneration of patient with diabetic retinopathy[J].Recent Advances in Ophthalmology,2020,40(10):392.[doi:10.13389/j.cnki.rao.2020.0091]
[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(10):677.[doi:10.13389/j.cnki.rao.2020.0156]
[14]姚国敏,李蓉,闫红林,等.高糖诱导的视网膜新生血管形成中NLRP3炎症小体与自噬的关系研究[J].眼科新进展,2020,40(8):706.[doi:10.13389/j.cnki.rao.2020.0161]
　YAO Guomin,LI Rong,YAN Honglin,et al.Relationship between NLRP3 inflammasome and autophagy in high-glucose induced retinal angiogenesis[J].Recent Advances in Ophthalmology,2020,40(10):706.[doi:10.13389/j.cnki.rao.2020.0161]

备注/Memo

备注/Memo:
国家自然科学基金资助（编号：81500711）；黑龙江省自然科学基金资助（编号：QC2015094）
更新日期/Last Update: 2019-10-12