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白藜芦醇通过降低慢性炎症和改善非肥胖型糖尿病小鼠的血糖记忆效应来预防糖尿病肾病。

Resveratrol prevents diabetic nephropathy by reducing chronic inflammation and improving the blood glucose memory effect in non-obese diabetic mice.

机构信息

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Department of Endocrinology, Liaocheng City People's Hospital, Liaocheng, Shandong, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2020 Oct;393(10):2009-2017. doi: 10.1007/s00210-019-01777-1. Epub 2020 Jan 22.

DOI:10.1007/s00210-019-01777-1
PMID:31970441
Abstract

Chronic inflammation plays an important role in the development of diabetic nephropathy. Advanced glycation end product receptor (RAGE), nuclear factor kappa B (NF-κB) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) are involved in the development of inflammation. Resveratrol is a plant antitoxin; it is believed to have anti-inflammatory effects and can improve blood glucose. We speculate that resveratrol treatment can protect renal function by reducing blood glucose, decreasing the expression of inflammatory factors. Non-obese diabetic (NOD) mice were randomly divided into three groups: T1DM, insulin (INS) and resveratrol (Res) groups. Mice without diabetes were classified as the non-diabetic control group (NOD-C group). The blood glucose (BG) level, blood urea nitrogen (BUN) level, serum creatinine (SCr) level and 24-h urinary microalbumin quantitative (UMA) were measured. The glomerulosclerosis index and basement membrane thickness were calculated under light and electron microscopes. The expression levels of RAGE, NF-кB (P65) and NOX4 in renal tissues were detected by Western blot analysis. We found that resveratrol treatment significantly reduced blood glucose within 28 days of the experiment, but the hypoglycemic effect was not lasting. At the same time, resveratrol reduced BUN, SCr, 24 h UMA and the expression of the inflammatory factors RAGE, NF-кB (P65) and NOX4 and improved the renal pathological structure. We believe that resveratrol improves renal function not only by its anti-inflammatory effect but also by improving the metabolic memory of hyperglycemia.

摘要

慢性炎症在糖尿病肾病的发生发展中起着重要作用。晚期糖基化终末产物受体(RAGE)、核因子 kappa B(NF-κB)和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶 4(NOX4)参与了炎症的发生。白藜芦醇是一种植物抗毒素,据信具有抗炎作用,并能改善血糖。我们推测,白藜芦醇治疗可以通过降低血糖、减少炎症因子的表达来保护肾功能。非肥胖型糖尿病(NOD)小鼠被随机分为三组:T1DM、胰岛素(INS)和白藜芦醇(Res)组。无糖尿病的小鼠被归类为非糖尿病对照组(NOD-C 组)。测量血糖(BG)水平、血尿素氮(BUN)水平、血清肌酐(SCr)水平和 24 小时尿微量白蛋白定量(UMA)。在光镜和电镜下计算肾小球硬化指数和基底膜厚度。通过 Western blot 分析检测肾组织中 RAGE、NF-κB(P65)和 NOX4 的表达水平。我们发现,白藜芦醇治疗在实验的 28 天内显著降低了血糖,但降糖作用并不持久。同时,白藜芦醇降低了 BUN、SCr、24 小时 UMA 以及炎症因子 RAGE、NF-κB(P65)和 NOX4 的表达,改善了肾脏的病理结构。我们认为,白藜芦醇改善肾功能不仅通过其抗炎作用,还通过改善高血糖的代谢记忆。

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