白藜芦醇通过上调miR-26a改善高糖诱导的人视网膜色素上皮细胞损伤

doi:10.12092/j.issn.1009-2501.2020.03.007

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (3): 285-292.doi: 10.12092/j.issn.1009-2501.2020.03.007

白藜芦醇通过上调miR-26a改善高糖诱导的人视网膜色素上皮细胞损伤

周海艳，王开玲

恩施土家族苗族自治州中心医院眼科中心，恩施 445000，湖北

收稿日期:2019-10-17 修回日期:2020-02-21 出版日期:2020-03-26 发布日期:2020-04-13
通讯作者: 王开玲，女，本科，主治医师，主要研究眼部疾病。 E-mail: 365147125@qq.com
作者简介:周海艳，女，本科，主治医师，主要研究眼部疾病。 Tel: 13597819196 E-mail: 786766879@qq.com
基金资助:
湖北省卫生计生西医类项目（WJ2015MA027）

Resveratrol protects human retinal pigment epithelial cells from toxicity of high glucose by up-regulation of miR-26a

ZHOU Haiyan, WANG Kailing

Eye Center of the Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, Hubei, China

Received:2019-10-17 Revised:2020-02-21 Online:2020-03-26 Published:2020-04-13

摘要/Abstract

摘要： 目的:研究白藜芦醇（RES）对高糖诱导的人视网膜色素上皮细胞ARPE-19损伤的保护机制。方法:高葡萄糖（HG）刺激ARPE-19细胞诱导建立损伤模型。分别采用细胞计数试剂盒-8（CCK-8）实验检测细胞活力、流式细胞术检测细胞凋亡率、DCFH-DA染色流式细胞仪检测活性氧（ROS）生成和定量即时聚合酶链锁反应（RT-qPCR）技术检测miR-26a表达水平。Western blot方法分析相关蛋白表达水平。结果:HG刺激明显降低ARPE-19细胞活力，凋亡率升高及氧化应激损伤加重。RES改善HG诱导的ARPE-19细胞损伤；上调HG诱导的ARPE-19细胞中miR-26a表达，miR-26a沉默部分逆转了RES对HG诱导的ARPE-19细胞损伤的保护效应。另外，RES还可通过上调miR-26a表达降低细胞外调节蛋白激酶（ERK）和Wnt/β-catenin信号通路活化。结论:RES通过上调miR-26a表达，伴随抑制ERK和Wnt/β-catenin信号传导，改善HG诱导的ARPE-19细胞损伤。RES可能成为治疗糖尿病视网膜病变的药物。

关键词: 白藜芦醇, 高糖, 人视网膜色素上皮细胞, miR-26a

Abstract: AIM: To study the protective effects and mechanism of resveratrol (RES) on the injury of human retinal pigment epithelial cells (ARPE-19) induced by high glucose (HG). METHODS: ARPE-19 cells were cultured in HG to simulate injury. Cell viability, apoptosis, ROS generation and miR-26a level were examined by CCK-8 assay, flow cytometry assay, DCFH-DA staining and RT-qPCR, respectively. Expression of proteins associated with viability, apoptosis and oxidative stress was measured by Western blot analysis. In addition, the involvements of the ERK and Wnt/β-catenin pathways were analyzed by Western blot analysis.RESULTS:HG reduced cell viability while promoted apoptosis and oxidative stress in ARPE-19 cells. RES ameliorated HG-induced cell injury. The expression of miR-26a was up-regulated by RES in HG-treated cells, and miR-26a inhibition obviously reversed the effects of RES on HG-treated cells. Finally, we found the ERK and Wnt/β-catenin pathways were inhibited by RES through up-regulation of miR-26a. CONCLUSION: RES protected ARPE-19 cells against HG-induced injury through up-regulating miR-26a, along with inhibition of the ERK and Wnt/β-catenin pathways. RES might be a potential therapeutic drug for diabetic retinopathy.

Key words: resveratrol, high glucose, human retinal pigment epithelial cells, miR-26a

中图分类号:

周海艳，王开玲. 白藜芦醇通过上调miR-26a改善高糖诱导的人视网膜色素上皮细胞损伤[J]. 中国临床药理学与治疗学, 2020, 25(3): 285-292.

ZHOU Haiyan, WANG Kailing . Resveratrol protects human retinal pigment epithelial cells from toxicity of high glucose by up-regulation of miR-26a[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(3): 285-292.

参考文献

［1］Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies［J］. JCI Insight, 2017, 2(5): e93751.
［2］Stitt AW, Curtis TM, Chen M, et al. The progress in understanding and treatment of diabetic retinopathy ［J］. Prog Retin Eye Res, 2016, 51(7): 156-186.
［3］Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy［J］. N Engl J Med, 2012, 366(4): 1227-1239.
［4］Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy ［J］. Diabetes Care, 2012, 35(7): 556-564.
［5］Datta S, Cano M, Ebrahimi K, et al. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD ［J］. Prog Retin Eye Res, 2017, 60(7): 201-218.
［6］Tien T, Barrette KF, Chronopoulos A, et al. Effects of high glucose-induced Cx43 downregulation on occludin and ZO-1 expression and tight junction barrier function in retinal endothelial cells ［J］. Invest Ophthalmol Vis Sci, 2013, 54(8): 6518-6525.
［7］Garcia-Medina JJ, Monica d-R-V, Garcia-Medina M, et al. Chapter 4-diabetic retinopathy and oxidative stress. In: Preedy VR, editor. Diabetes: Oxidative Stress and Dietary Antioxidants ［M］. San Diego: Academic Press; 2014. p. 33-40.
［8］Lutty GA. Effects of diabetes on the eye ［J］. Invest Ophthalmol Vis Sci, 2013, 54(8): 81-87.
［9］宋娟, 田小霞, 李宝红, 等. 白藜芦醇对去卵巢骨质疏松大鼠Wnt/β-Catenin通路的影响［J］. 中国临床药理学与治疗学, 2017, 22(5): 138-141.
［10］Zhou C, Ding J, Wu Y. Resveratrol induces apoptosis of bladder cancer cells via miR 21 regulation of the Akt/Bcl 2 signaling pathway ［J］. Mol Med Rep, 2014, 9(4): 1467-1473.
［11］Noh KT, Chae SH, Chun SH, et al. Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase［J］. Biochem Biophys Res Commun, 2013, 431(2): 348-353.
［12］Sareen D, van Ginkel PR, Takach JC, et al. Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells ［J］. Invest Ophthalmol Vis Sci, 2006, 47(9): 1132-1144.
［13］杨影, 吴峥峥, 程依琏, 等. 白藜芦醇对过氧化氢诱导人视网膜色素上皮细胞凋亡的保护作用［J］. 实用医学杂志, 2018, 34(8): 1244-1247.
［14］Shi H, Zhang Z, Wang X, et al. Inhibition of autophagy induces IL-1beta release from ARPE-19 cells via ROS mediated NLRP3 inflammasome activation under high glucose stress ［J］. Biochem Biophys Res Commun, 2015, 463(7): 1071-1076.
［15］Mondal A, Bennett LL. Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage ［J］. Biomed Pharmacother, 2016, 84(7): 1906-1914.
［16］Liu WY, Liou SS, Hong TY, et al. Hesperidin prevents high glucose-induced damage of retinal pigment epithelial cells ［J］. Planta Med, 2018, 31(7): 1209-1216.
［17］Liu J, Zhang C, Hu W, et al. Tumor suppressor p53 and its mutants in cancer metabolism ［J］. Cancer Lett, 2015, 356(7): 197-203.
［18］Galanos P, Vougas K, Walter D. Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing ［J］. Nature, 2016, 18(7): 777-789.
［19］Sharma S, Saxena S, Srivastav K, et al. Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations ［J］. Clin Exp Ophthalmol, 2015, 43(6): 429-436.
［20］Lopez MS, Dempsey RJ, Vemuganti R, et al. Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles ［J］. J Cereb Blood Flow Metab, 2016, 36(9): 201-213.
［21］Xu XH, Ding DF, Yong HJ, et al. Resveratrol transcriptionally regulates miRNA- 18a- 5p expression ameliorating diabetic nephropathy via increasing autophagy［J］. Eur Rev Med Pharmacol Sci, 2017, 21(21): 109-116.
［22］Gracia A, Fernández-Quintela A, Miranda J, et al. Are miRNA-103,miRNA-107 and miRNA-122 involved in the prevention of liver steatosis induced by resveratrol［J］. Nutrients, 2017, 9(4): 209-216.
［23］Gong Y, Wu W, Zou X, et al. MiR-26a inhibits thyroid cancer cell proliferation by targeting ARPP19 ［J］. Am J Cancer Res, 2018, 8(4): 1030-1039.
［24］Buckner CA, Buckner AL, Koren SA, et al. Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells ［J］. Nutrients, 2018, 39(9): 217-230.
［25］Liu Y, Li X, Jiang S, et al. Tetramethylpyrazine protects against high glucose-induced vascular smooth muscle cell injury through inhibiting the phosphorylation of JNK, p38MAPK, and ERK［J］. J Cereb Blood Flow Metab, 2018, 46(7): 3318-3326.
［26］Garcia-Jimenez C, Garcia-Martinez JM, Chocarro-Calvo A, et al. A new link between diabetes and cancer: enhanced WNT/beta-catenin signaling by high glucose ［J］. J Mol Endocrinol, 2014, 52(7): R51-66.

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白藜芦醇通过上调miR-26a改善高糖诱导的人视网膜色素上皮细胞损伤

Resveratrol protects human retinal pigment epithelial cells from toxicity of high glucose by up-regulation of miR-26a

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