Tert-butylhydroquinone promotes skin flap survival by inhibiting oxidative stress mediated by the Nrf2/HO-1 signalling pathway

IF 6.8 2区医学 Q1 PHARMACOLOGY & PHARMACY

British Journal of Pharmacology Pub Date : 2024-09-04 DOI:10.1111/bph.17321

Kaitao Wang, An Wang, Jiapeng Deng, Jialong Yang, Guodong Chen, Qingyu Chen, Minle Ye, Dingsheng Lin

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引用次数: 0

Abstract

Background and Purpose

Skin flaps are among the most important means of wound repair in clinical settings. However, partial or even total distal necrosis may occur after a flap operation, with severe consequences for both patients and doctors. This study investigated whether tert-butylhydroquinone (TBHQ), a known agonist of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), and an antioxidant, could promote skin flap survival.

Experimental Approach

McFarlane skin flap models were established in male Sprague–Dawley rats and then randomly divided into control, low-dose TBHQ, and high-dose TBHQ treatment groups. On postoperative day 7, the survival and blood flow of the skin flaps were assessed. Using flap tissue samples, angiogenesis, inflammation, apoptosis, autophagy, and Nrf2/haem oxygenase 1 (HO-1) signalling pathway activity were measured with immunohistochemical techniques and western blotting.

Key Results

TBHQ dose-dependently stimulated the Nrf2/HO-1 signalling pathway, inducing autophagy through the up-regulation of LC3B and beclin 1 and concurrently suppressing p62 expression. Additionally, TBHQ hindered apoptosis by enhancing Bcl-2 expression while inhibiting the expression of Bax. It suppressed inflammation by inhibiting the expression of interleukin 1β, interleukin 6, and tumour necrosis factor-α and enhanced angiogenesis by promoting the expression of vascular endothelial growth factor.

Conclusion and Implications

In summary, TBHQ promoted flap survival in rats by up-regulating the Nrf2/HO-1 signalling pathway. As TBHQ is already widely used as a food additive, it could offer an acceptable means of improving clinical outcomes following skin flap surgery in patients.

Abstract Image

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叔丁基对苯二酚通过抑制 Nrf2/HO-1 信号通路介导的氧化应激促进皮瓣存活。

背景和目的：皮瓣是临床上最重要的伤口修复手段之一。然而，皮瓣手术后可能会出现部分甚至全部远端坏死，给患者和医生带来严重后果。本研究探讨了叔丁基对苯二酚（TBHQ）--一种已知的转录因子核因子红细胞2相关因子2（Nrf2）激动剂和抗氧化剂--能否促进皮瓣存活：实验方法：用雄性 Sprague-Dawley 大鼠建立麦克法兰皮瓣模型，然后将其随机分为对照组、低剂量 TBHQ 治疗组和高浓度 TBHQ 治疗组。术后第 7 天，对皮瓣的存活率和血流量进行评估。利用皮瓣组织样本，采用免疫组化技术和 Western 印迹法测定血管生成、炎症、细胞凋亡、自噬和 Nrf2/ 血氧合酶 1（HO-1）信号通路的活性：主要结果：TBHQ剂量依赖性地刺激Nrf2/HO-1信号通路，通过上调LC3B和beclin 1诱导自噬，同时抑制p62的表达。此外，TBHQ 还能提高 Bcl-2 的表达，同时抑制 Bax 的表达，从而阻碍细胞凋亡。它通过抑制白细胞介素 1β、白细胞介素 6 和肿瘤坏死因子-α的表达来抑制炎症，并通过促进血管内皮生长因子的表达来增强血管生成：总之，TBHQ 通过上调 Nrf2/HO-1 信号通路促进了大鼠皮瓣的存活。由于 TBHQ 已被广泛用作食品添加剂，因此它可以为改善患者皮瓣手术后的临床疗效提供一种可接受的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British Journal of Pharmacology 医学-药学

CiteScore

15.40

自引率

12.30%

发文量

270

审稿时长

2.0 months

期刊介绍： The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries. Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues. In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.