• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

白藜芦醇减轻 1 型糖尿病小鼠睾丸细胞凋亡： Akt 介导的 Nrf2 激活和 p62 依赖性 Keap1 降解的作用。

Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: Role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation.

机构信息

Cancer Center, the First Hospital of Jilin University, Changchun, Jilin 130021, China.

Department of Spinal Surgery, the First Hospital of Jilin University, Changchun, Jilin 130021, China.

出版信息

Redox Biol. 2018 Apr;14:609-617. doi: 10.1016/j.redox.2017.11.007. Epub 2017 Nov 8.

DOI:10.1016/j.redox.2017.11.007
PMID:29154192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5975057/
Abstract

Infertility is a common complication in diabetic men, mainly due to the loss of germ cells by apoptotic cell death. However, effective and safe approaches to prevent diabetic induction of testicular apoptosis for diabetic patients have not been available. Resveratrol (RSV), a group of compounds called polyphenols from plants, has been indicated its promising used clinically for cancers and cardiovascular diseases. Therefore, the present study aimed determining whether RSV attenuates type 1 diabetes (T1D)-induced testicular apoptotic cell death in a mouse model. We found that testicular apoptosis and oxidative stress levels were significantly higher in T1D mice than control mice. In addition, the phosphorylation level of metabolism-related Akt and GSK-3β was downregulated and Akt negative regulators PTEN, PTP1B and TRB3 were upregulated in the T1D group. These effects were partially prevented by RSV treatment. Nrf2 and its downstream genes, such as NQO-1, HO-1, SOD, catalase and metallothionein were significantly upregulated by RSV treatment. In addition, RSV-induced Nrf2 activation was found due to Keap1 degradation, mainly reliant on p62 that functions as an adaptor protein during autophagy. These results indicate that the attenuation of T1D-induced testicular oxidative stress and apoptosis by RSV treatment was mainly related to Akt-mediated Nrf2 activation via p62-dependent Keap1 degradation.

摘要

不育症是糖尿病男性的常见并发症，主要是由于生殖细胞通过细胞凋亡而丧失。然而，对于糖尿病患者，还没有有效的、安全的方法来预防糖尿病诱导的睾丸细胞凋亡。白藜芦醇（Resveratrol，RSV）是一种植物来源的多酚类化合物，已被证明在癌症和心血管疾病的临床治疗中有很大的应用前景。因此，本研究旨在确定 RSV 是否可以减轻 1 型糖尿病（T1D）诱导的小鼠睾丸细胞凋亡。我们发现，与对照组相比，T1D 组的睾丸细胞凋亡和氧化应激水平明显更高。此外，T1D 组的代谢相关 Akt 和 GSK-3β的磷酸化水平下调，Akt 的负调节因子 PTEN、PTP1B 和 TRB3 上调。RSV 治疗部分阻止了这些变化。Nrf2 及其下游基因，如 NQO-1、HO-1、SOD、过氧化氢酶和金属硫蛋白，在 RSV 治疗后显著上调。此外，我们发现 RSV 诱导的 Nrf2 激活是由于 Keap1 降解引起的，主要依赖于 p62，它在自噬过程中作为一种衔接蛋白发挥作用。这些结果表明，RSV 治疗减轻 T1D 诱导的睾丸氧化应激和细胞凋亡主要与 Akt 介导的 Nrf2 激活有关，这种激活是通过 p62 依赖的 Keap1 降解来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/8df56cc7da52/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/7ef1634f303d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/65b562d9736a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/48e31ed3a398/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/006fe9758fdf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/cc163ec8f0fd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/cd0a3b741aa5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/8df56cc7da52/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/7ef1634f303d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/65b562d9736a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/48e31ed3a398/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/006fe9758fdf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/cc163ec8f0fd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/cd0a3b741aa5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/5975057/8df56cc7da52/gr6.jpg

相似文献

1
Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: Role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation.白藜芦醇减轻 1 型糖尿病小鼠睾丸细胞凋亡： Akt 介导的 Nrf2 激活和 p62 依赖性 Keap1 降解的作用。
Redox Biol. 2018 Apr;14:609-617. doi: 10.1016/j.redox.2017.11.007. Epub 2017 Nov 8.
2
Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation.反复低剂量X射线照射可减轻2型糖尿病大鼠的睾丸细胞凋亡，可能是通过Akt介导的Nrf2激活实现的。
Mol Cell Endocrinol. 2016 Feb 15;422:203-210. doi: 10.1016/j.mce.2015.12.012. Epub 2015 Dec 17.
3
Allopurinol reduces oxidative stress and activates Nrf2/p62 to attenuate diabetic cardiomyopathy in rats.别嘌醇可减少氧化应激并激活 Nrf2/p62 以减轻大鼠糖尿病心肌病。
J Cell Mol Med. 2020 Jan;24(2):1760-1773. doi: 10.1111/jcmm.14870. Epub 2019 Dec 19.
4
p62/SQSTM1 protects against cisplatin-induced oxidative stress in kidneys by mediating the cross talk between autophagy and the Keap1-Nrf2 signalling pathway.p62/SQSTM1 通过介导自噬与 Keap1-Nrf2 信号通路的串扰，保护肾脏免受顺铂诱导的氧化应激。
Free Radic Res. 2019 Jul;53(7):800-814. doi: 10.1080/10715762.2019.1635251. Epub 2019 Jul 8.
5
Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity.p62和Nrf2的协同作用保护细胞免受棕榈酸诱导的脂毒性。
Biochem Biophys Res Commun. 2015 Oct 9;466(1):131-7. doi: 10.1016/j.bbrc.2015.08.120. Epub 2015 Aug 30.
6
TAK1 Regulates the Nrf2 Antioxidant System Through Modulating p62/SQSTM1.TAK1通过调节p62/SQSTM1来调控Nrf2抗氧化系统。
Antioxid Redox Signal. 2016 Dec 10;25(17):953-964. doi: 10.1089/ars.2016.6663. Epub 2016 Jun 30.
7
p62/SQSTM1 is required for the protection against endoplasmic reticulum stress-induced apoptotic cell death.p62/SQSTM1是抵御内质网应激诱导的凋亡性细胞死亡所必需的。
Free Radic Res. 2016 Dec;50(12):1408-1421. doi: 10.1080/10715762.2016.1253073. Epub 2016 Nov 23.
8
Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function.莱菔硫烷通过上调 Nrf2 的表达和功能对 1 型糖尿病诱导的睾丸细胞凋亡起保护作用。
Toxicol Appl Pharmacol. 2014 Sep 1;279(2):198-210. doi: 10.1016/j.taap.2014.06.009. Epub 2014 Jun 23.
9
Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.褪黑素通过自噬调控的 p62/Keap1/Nrf2 通路减轻 10-羟基喜树碱诱导的小鼠睾丸细胞氧化应激和凋亡。
J Pineal Res. 2024 May;76(4):e12959. doi: 10.1111/jpi.12959.
10
PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1.PF-4708671，一种p70核糖体S6激酶1的特异性抑制剂，通过促进Keap1的p62依赖性自噬降解来激活Nrf2。
Biochem Biophys Res Commun. 2015 Oct 23;466(3):499-504. doi: 10.1016/j.bbrc.2015.09.059. Epub 2015 Sep 14.

引用本文的文献

1
Taxifolin and Astilbin Protect Against Cadmium-Induced Oxidative Stress and Apoptosis in Chicken Liver Cells via Nrf2/HO-1 Signaling.紫杉叶素和落新妇苷通过Nrf2/HO-1信号通路保护鸡肝细胞免受镉诱导的氧化应激和细胞凋亡。
Biol Trace Elem Res. 2025 Aug 29. doi: 10.1007/s12011-025-04802-y.
2
β-Glucan and resveratrol mitigate lead induced reproductive toxicity in male mice.β-葡聚糖和白藜芦醇可减轻铅对雄性小鼠生殖系统的毒性。
Sci Rep. 2025 Aug 25;15(1):31277. doi: 10.1038/s41598-025-16510-7.
3
Mechanisms Linking Obesity, Insulin Resistance, and Alzheimer's Disease: Effects of Polyphenols and Omega-3 Polyunsaturated Fatty Acids.

本文引用的文献

1
Resveratrol ameliorates benzo(a)pyrene-induced testicular dysfunction and apoptosis: involvement of p38 MAPK/ATF2/iNOS signaling.白藜芦醇改善苯并(a)芘诱导的睾丸功能障碍和细胞凋亡：p38丝裂原活化蛋白激酶/活化转录因子2/诱导型一氧化氮合酶信号通路的参与
J Nutr Biochem. 2016 Aug;34:17-29. doi: 10.1016/j.jnutbio.2016.04.003. Epub 2016 Apr 25.
2
Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation.反复低剂量X射线照射可减轻2型糖尿病大鼠的睾丸细胞凋亡，可能是通过Akt介导的Nrf2激活实现的。
Mol Cell Endocrinol. 2016 Feb 15;422:203-210. doi: 10.1016/j.mce.2015.12.012. Epub 2015 Dec 17.
3
连接肥胖、胰岛素抵抗和阿尔茨海默病的机制：多酚和ω-3多不饱和脂肪酸的作用
Nutrients. 2025 Mar 29;17(7):1203. doi: 10.3390/nu17071203.
4
Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway.白藜芦醇通过调节NRF2-SLC7A11-GPX4通路减轻抗PD-1诱导的睾丸毒性。
Front Immunol. 2025 Mar 12;16:1529991. doi: 10.3389/fimmu.2025.1529991. eCollection 2025.
5
Resveratrol: potential application in safeguarding testicular health.白藜芦醇：在维护睾丸健康方面的潜在应用。
EPMA J. 2024 Sep 2;15(4):643-657. doi: 10.1007/s13167-024-00377-1. eCollection 2024 Dec.
6
Testicular immunity.睾丸免疫
Mol Aspects Med. 2024 Dec;100:101323. doi: 10.1016/j.mam.2024.101323. Epub 2024 Nov 25.
7
Exploring the impact of lipid stress on sperm cytoskeleton: insights and prospects.探索脂质应激对精子细胞骨架的影响：见解与展望。
Nat Rev Urol. 2025 May;22(5):294-312. doi: 10.1038/s41585-024-00952-1. Epub 2024 Nov 11.
8
From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes.从清除 ROS 到增强的骨整合：含铈介孔生物活性玻璃纳米颗粒功能化植入物在糖尿病中的应用。
J Nanobiotechnology. 2024 Oct 18;22(1):639. doi: 10.1186/s12951-024-02865-y.
9
Wharton's Jelly Mesenchymal Stem Cell Conditioned Medium Ameliorates Diabetes-Induced Testicular Damage and Sperm Abnormalities by Mitigating Oxidative Stress, Apoptosis, and Inflammation.沃顿胶间充质干细胞条件培养基通过减轻氧化应激、细胞凋亡和炎症来改善糖尿病诱导的睾丸损伤和精子异常。
Stem Cells Int. 2024 Oct 3;2024:7084913. doi: 10.1155/2024/7084913. eCollection 2024.
10
Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.非传染性疾病中的天然自噬调节剂：从自噬机制到治疗潜力
Acta Pharmacol Sin. 2025 Jan;46(1):8-32. doi: 10.1038/s41401-024-01356-y. Epub 2024 Aug 1.
Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells.
PI3K/Akt/Nrf2 信号通路在迷迭香酸对甲基乙二醛诱导的 SH-SY5Y 神经母细胞瘤细胞神经毒性的保护作用中的作用。
Chem Biol Interact. 2015 Dec 5;242:396-406. doi: 10.1016/j.cbi.2015.11.003. Epub 2015 Nov 12.
4
PI3K-AKT Signaling via Nrf2 Protects against Hyperoxia-Induced Acute Lung Injury, but Promotes Inflammation Post-Injury Independent of Nrf2 in Mice.通过Nrf2的PI3K-AKT信号传导可预防高氧诱导的急性肺损伤，但在小鼠中，损伤后会独立于Nrf2促进炎症反应。
PLoS One. 2015 Jun 15;10(6):e0129676. doi: 10.1371/journal.pone.0129676. eCollection 2015.
5
Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1-independent manner.白藜芦醇治疗以不依赖sirt1的方式恢复糖尿病小鼠的外周胰岛素敏感性。
Mol Nutr Food Res. 2015 Aug;59(8):1431-42. doi: 10.1002/mnfr.201400933. Epub 2015 Apr 28.
6
Repair of orbital implant exposure using Müller's muscle flap.使用米勒肌瓣修复眼眶植入物暴露
J Fr Ophtalmol. 2014 Oct;37(8):618-22. doi: 10.1016/j.jfo.2014.04.006. Epub 2014 Sep 26.
7
Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function.蒜硫胺素降低糖尿病小鼠睾丸细胞凋亡与 Nrf2 表达和功能的上调有关。
Am J Physiol Endocrinol Metab. 2014 Jul 1;307(1):E14-23. doi: 10.1152/ajpendo.00702.2013. Epub 2014 May 6.
8
Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.在糖尿病条件下，锌对于体外培养的人肾小管细胞以及体内小鼠肾脏中Nrf2的转录功能至关重要。
J Cell Mol Med. 2014 May;18(5):895-906. doi: 10.1111/jcmm.12239. Epub 2014 Mar 6.
9
The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K(+) channels.白藜芦醇对未孕大鼠子宫收缩性的影响：钾通道的作用
J Physiol Pharmacol. 2013 Dec;64(6):795-805.
10
Regulation of Nrf2-an update.Nrf2 的调控机制——最新进展。
Free Radic Biol Med. 2014 Jan;66:36-44. doi: 10.1016/j.freeradbiomed.2013.02.008. Epub 2013 Feb 19.