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香草醛通过调节Nrf2和ZO-1对应激诱导的生精小管损伤可能具有的保护作用。

Possible protective effects of vanillin against stress-induced seminiferous tubule injury via modulation of Nrf2 and ZO1.

作者信息

Abdel Hafez Sara Mohamed Naguib, Saber Entesar Ali, Aziz Neven Makram, Aleem Mohammed Mustafa Abd El, Mohamed Manar Samir, Abdelhafez Elshimaa M N, Ibrahim Randa Ahmed

机构信息

Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia, Egypt.

Department of Medical Sciences (Histology and Cell Biology), Deraya University, New Minia City, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1853-1870. doi: 10.1007/s00210-024-03355-6. Epub 2024 Aug 26.

DOI:10.1007/s00210-024-03355-6
PMID:39186188
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11825570/
Abstract

Around 20% of the human population is distressed. Previous studies have looked into the relationship between restraint immobilization stress (IS) and sexual behavior in male rats. The current study aimed to provide a brief explanation of the mechanisms that generated testicular injury with chronic IS and an attempt to evaluate the mechanisms and effects of vanillin as a novel protective agent. Forty-eight adult male albino rats were divided into six groups: control, vanillin-treated, chronic 2-h IS, 2-h stressed-vanillin-treated, chronic 6-h IS, and 6-h stressed-vanillin treated. The rats were sacrificed, and blood samples were collected for biochemical study. The testes were processed for biochemical and histological study, as well as histological Johnsen score. The results showed that prolonged IS increased both corticosterone and TNF-α levels as well as decreased testosterone, luteinizing hormone, catalase, and Nrf2 levels. This effect was more pronounced after 6 h of IS compared to 2 h. It also induced various testicular injuries with weak ZO-1 and CD34 immunoreactions. On the contrary, vanillin improved all mentioned biochemical and histological alternations induced by stress. Additionally, computational molecular docking analyses were conducted on the compound vanillin within the active site of Zona Occludens-1 (PDB ID: 2JWE). The results demonstrated remarkable docking scores and binding affinity, corroborating its potential protective efficacy. It could be concluded that vanillin is a promising treatment alternative for protecting testicular tissue from the harmful effects of IS via its antioxidant and anti-inflammatory properties.

摘要

大约20%的人类处于痛苦之中。先前的研究探讨了束缚制动应激(IS)与雄性大鼠性行为之间的关系。本研究旨在简要解释慢性IS导致睾丸损伤的机制,并尝试评估香草醛作为一种新型保护剂的作用机制和效果。48只成年雄性白化大鼠被分为六组:对照组、香草醛处理组、慢性2小时IS组、2小时应激-香草醛处理组、慢性6小时IS组和6小时应激-香草醛处理组。处死大鼠并采集血样进行生化研究。对睾丸进行生化、组织学研究以及组织学约翰森评分。结果表明,长时间的IS会增加皮质酮和TNF-α水平,同时降低睾酮、促黄体生成素、过氧化氢酶和Nrf2水平。与2小时相比,6小时的IS后这种影响更为明显。它还会引发各种睾丸损伤,伴有ZO-1和CD34免疫反应减弱。相反,香草醛改善了应激诱导的所有上述生化和组织学变化。此外,还对紧密连接蛋白-1(PDB ID:2JWE)活性位点内的香草醛化合物进行了计算分子对接分析。结果显示出显著的对接分数和结合亲和力,证实了其潜在的保护功效。可以得出结论,香草醛通过其抗氧化和抗炎特性,有望成为保护睾丸组织免受IS有害影响的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/fc73425df055/210_2024_3355_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/fc73425df055/210_2024_3355_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/03d7fb9cc3c8/210_2024_3355_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/5c00122a3d17/210_2024_3355_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/1320647d492a/210_2024_3355_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/cb84086cf364/210_2024_3355_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/9a68572a5dd8/210_2024_3355_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/f3ddd2fa6e12/210_2024_3355_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/0216c423964b/210_2024_3355_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/39c414e654f4/210_2024_3355_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5cb/11825570/fc73425df055/210_2024_3355_Fig9_HTML.jpg

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本文引用的文献

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What do we know about blood-testis barrier? current understanding of its structure and physiology.我们对血睾屏障了解多少?对其结构和生理学的当前认识。
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Vanillin attenuates the ethanol withdrawal syndrome and ethanol withdrawal induced anxiety by regulating the neurochemical balance.
香草醛通过调节神经化学平衡减轻乙醇戒断综合征和乙醇戒断诱导的焦虑。
Folia Neuropathol. 2022;60(3):316-323. doi: 10.5114/fn.2022.118546.
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Behavior and Functional Roles of CD34 Mesenchymal Cells in Mammalian Testes.CD34 间质细胞在哺乳动物睾丸中的行为和功能作用。
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Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats.香草酸和维生素 C 可减轻邻苯二甲酸二(2-乙基己基)酯对成年雄性大鼠睾丸的毒性。
Reprod Fertil. 2022 Sep 26;3(3):220-230. doi: 10.1530/RAF-22-0045. Print 2022 Jul 1.
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Immobilization stress exacerbates arsenic-induced reprotoxic effects in adult rats.制动应激会加剧成年大鼠体内砷诱导的生殖毒性作用。
Toxicol Res (Camb). 2022 May 9;11(3):426-436. doi: 10.1093/toxres/tfac022. eCollection 2022 Jun.
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Vanillin exerts therapeutic effects against hyperglycemia-altered glucose metabolism and purinergic activities in testicular tissues of diabetic rats.香草醛可对抗糖尿病大鼠睾丸组织中高血糖引起的糖代谢紊乱和嘌呤能活性改变,发挥治疗作用。
Reprod Toxicol. 2021 Jun;102:24-34. doi: 10.1016/j.reprotox.2021.03.007. Epub 2021 Apr 3.
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Chronic unpredictable stress disturbs the blood-testis barrier affecting sperm parameters in mice.慢性不可预测应激会破坏血睾屏障,影响小鼠的精子参数。
Reprod Biomed Online. 2021 May;42(5):983-995. doi: 10.1016/j.rbmo.2020.12.007. Epub 2021 Feb 16.
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Identification of telocytes in dystrophic mice testis.营养不良小鼠睾丸中睾丸间质细胞的鉴定。
Einstein (Sao Paulo). 2021 Jan 25;19:eAI5737. doi: 10.31744/einstein_journal/2021AI5737. eCollection 2021.
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