The impact of chitooligosaccharides with a certain degree of polymerization on diabetic nephropathic mice and high glucose-damaged HK-2 cells

IF 3.5 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Food Science & Nutrition Pub Date : 2024-03-22 DOI:10.1002/fsn3.4078

Yuwen Liu, Ran Zhang, Jiaqi Zou, Hao Yin, Mengyao Zhao, Liming Zhao

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Abstract

Diabetic nephropathy (DN) is a primary diabetic complication ascribed to the pathological changes in renal microvessels. This study investigated the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch ECH associating protein (Keap1)/antioxidant response element (ARE) signaling pathway impact of chitooligosaccharides (COS) with a certain degree of polymerization (DP) on DN mouse models and high glucose-damaged human kidney 2 (HK-2) cells. The findings indicated that COS effectively reduced the renal function indexes (uric acid [UA], urinary albumin excretion rate [UAER], urine albumin-to-creatinine ratio [UACR], blood urea nitrogen [BUN], and creatinine [Cre]) of DN mice. It increased (p < .05) the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) antioxidant enzyme activity in the serum and kidneys, and decreased (p < .05) the malondialdehyde (MDA) content. The mechanistic investigation showed that COS significantly increased (p < .05) Nrf2 and downstream target gene (GCLM, GCLC, HO-1, and NQO-1) expression, and substantially decreased (p < .05) Keap1 expression. The protein level was consistent with the messenger RNA (mRNA) level in in vitro and in vivo models. The docking data indicated that COS and Keap1 protein binding included six hydrogen bond formation processes (Gly364, Arg415, Arg483, His436, Ser431, and Arg380). The COS intervention mechanism may be related to the Nrf2/Keap1/ARE antioxidant pathway. Therefore, it provides a scientific basis for COS application in developing special medical food for DN patients.

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具有一定聚合度的壳寡糖对糖尿病肾病小鼠和高糖损伤的 HK-2 细胞的影响

糖尿病肾病（DN）是一种主要的糖尿病并发症，是由肾脏微血管的病理变化引起的。本研究探讨了具有一定聚合度（DP）的壳寡糖（COS）对DN小鼠模型和高糖损伤的人肾2（HK-2）细胞的核因子红细胞2相关因子2（Nrf2）/Kelch ECH关联蛋白（Keap1）/抗氧化反应元件（ARE）信号通路的影响。研究结果表明，COS 能有效降低 DN 小鼠的肾功能指标（尿酸[UA]、尿白蛋白排泄率[UAER]、尿白蛋白与肌酐比值[UACR]、血尿素氮[BUN]和肌酐[Cre]）。它能提高（p < .05）血清和肾脏中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的抗氧化酶活性，降低（p < .05）丙二醛（MDA）含量。机理研究表明，COS 能显著提高（p < .05）Nrf2 及其下游靶基因（GCLM、GCLC、HO-1 和 NQO-1）的表达，并大幅降低（p < .05）Keap1 的表达。在体外和体内模型中，蛋白质水平与信使 RNA（mRNA）水平一致。对接数据表明，COS 与 Keap1 蛋白的结合包括六个氢键形成过程（Gly364、Arg415、Arg483、His436、Ser431 和 Arg380）。COS 的干预机制可能与 Nrf2/Keap1/ARE 抗氧化途径有关。因此，这为将 COS 应用于开发 DN 患者专用医疗食品提供了科学依据。

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来源期刊

Food Science & Nutrition Agricultural and Biological Sciences-Food Science

CiteScore

7.40

自引率

5.10%

发文量

434

审稿时长

24 weeks

期刊介绍： Food Science & Nutrition is the peer-reviewed journal for rapid dissemination of research in all areas of food science and nutrition. The Journal will consider submissions of quality papers describing the results of fundamental and applied research related to all aspects of human food and nutrition, as well as interdisciplinary research that spans these two fields.