通过关注糖尿病大鼠肝脏中的Nrf2/Keap1/HO-1信号通路评估辅酶Q10对高血糖引起的氧化应激的抗氧化作用

IF 1.6 Q2 MEDICINE, GENERAL & INTERNAL Iranian Journal of Medical Sciences Pub Date : 2024-10-01 DOI:10.30476/ijms.2023.100078.3222
Fatemeh Samimi, Maryam Baazm, Zahra Nadi, Sanaz Dastghaib, Mehri Rezaei, Farideh Jalali-Mashayekhi
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引用次数: 0

摘要

背景:高血糖引起的氧化应激可损害肝脏,导致糖尿病并发症。辅酶 Q10(CoQ-10)可降低与糖尿病相关的氧化应激。然而,其分子机制仍不清楚。本研究旨在研究辅酶Q10对高血糖诱导的糖尿病大鼠肝脏氧化应激的抗氧化能力,特别是针对Nrf2/Keap1/ARE信号通路:本研究于 2020-2021 年在阿拉克医科大学进行。将 30 只体重 220-250 克的雄性成年 Wistar 大鼠(8 周大)随机分为 5 组(每组 6 只):健康对照组、芝麻油(CoQ-10 溶剂)组、CoQ-10(10 毫克/千克)组、糖尿病组和糖尿病+CoQ-10 组。采用分光光度法估算肝脏氧化应激指标,包括丙二醛、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽。采用实时 PCR 检测肝组织中 Nrf2、Keap1、HO-1 和 NQO1 基因的表达。所有治疗均持续 6 周。使用 SPSS 软件进行统计分析。采用单因素方差分析和 LSD 或 Tukey 后检验来比较不同组的结果。结果研究结果表明,与健康组相比,糖尿病诱导明显增加了 Keap1 的表达(2.1±0.9 倍,P=0.01),并显著抑制了 Nrf2(0.38±0.2 倍,P=0.009)、HO-1(0.27±0.1 倍,P=0.02)和 NQO1(0.26±0.1 倍,P=0.01)的 mRNA 表达。在糖尿病组中,谷胱甘肽过氧化物酶、过氧化氢酶的活性和谷胱甘肽水平降低,丙二醛水平升高。补充 CoQ-10 能明显上调 Nrf2(0.85±0.3,P=0.04)、HO-1(0.94±0.2,P=0.04)、NQO1(0.88±0.5,P=0.03)基因的表达,抑制 Keap1 的表达(1.1±0.6,P=0.02)。此外,与对照组糖尿病大鼠相比,CoQ-10能降低丙二醛水平,提高过氧化氢酶、谷胱甘肽过氧化物酶活性和治疗组大鼠肝组织中谷胱甘肽水平,从而改善氧化应激:本研究结果表明,CoQ-10 可通过调节 Nrf2/Keap1/HO-1/NQO1 信号通路提高糖尿病大鼠肝组织的抗氧化能力。
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Evaluation of Antioxidant Effects of Coenzyme Q10 against Hyperglycemia-Mediated Oxidative Stress by Focusing on Nrf2/Keap1/HO-1 Signaling Pathway in the Liver of Diabetic Rats.

Background: Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10's antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway.

Methods: This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD's or Tukey's post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant.

Results: The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNA expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group.

Conclusion: The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway.

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来源期刊
Iranian Journal of Medical Sciences
Iranian Journal of Medical Sciences MEDICINE, GENERAL & INTERNAL-
CiteScore
3.20
自引率
0.00%
发文量
84
审稿时长
12 weeks
期刊介绍: The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of com­muni­cation for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science re­search experiences on prevalent diseases in the region and analysis of various regional problems.
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