铁死亡在牙周炎中的作用：一项大鼠动物研究

Role of ferroptosis in periodontitis: An animal study in rats.

作者信息

Fu Earl, Kuo Chan-Yen, Hsia Yi-Jan, Huang Yiao-Mien, Tseng Hui-Hwa, Fu Min-Wen, Shih Kuang-Chung

机构信息

Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

出版信息

J Periodontal Res. 2023 Oct;58(5):1031-1040. doi: 10.1111/jre.13165. Epub 2023 Jul 21.

DOI:10.1111/jre.13165

PMID:37477155

Abstract

OBJECTIVE

This study aimed to investigate (1) the temporal pattern of ferroptosis, an iron-dependent cell death, in ligation-induced rat periodontitis and (2) the effect of ferrostatin-1, a ferroptosis inhibitor, on the model.

BACKGROUND

Ferroptosis may contribute to various diseases. However, the role of ferroptosis in periodontitis is still fully understood.

METHODS

In the first experiment, 25 rats with ligation-induced periodontitis were sacrificed on days 0, 1, 2, 7, and 10. Gingivae were obtained to determine tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and ferroptotic biomarkers, including solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (Gpx4), via immunoblotting. Using microcomputed tomography (μCT) and histology, the periodontal soft and hard tissue lesions, including dental alveolar bone crest level, bony characteristics of the surrounding alveolus, periodontal tissue inflammation, and periodontal tissue losses, were evaluated. In study two, 16 rats with induced periodontitis were grouped according to ferrostatin-1 treatment. The rats were intraperitoneally injected with solvent or ferrostatin-1 (1.5 mg/kg/day) 1 day before ligation and sacrificed on days 7 and 10. Gingival protein changes and periodontal tissue damage were also examined.

RESULTS

In study one, SLC3A2/SLC7A11 and Gpx4 decreased since day 1; however, TNF-α/IL-1β increased on days 7 and 10. Moreover, the μCT/histology revealed resorptive bony characteristics, inflamed gingival tissue, and periodontal attachment loss. In study two, ferrostatin-1-injected rats exhibited significantly increased SLC3A2/SLC7A11 and Gpx4 but decreased TNF-α/IL-1β than vehicle rats. They also revealed lessened bone resorption, tissue inflammation, and attachment loss.

CONCLUSION

This study highlights the role of ferroptosis, via the system Xc/Gpx4 pathway, in experimental periodontitis and may serve as a regulatory strategy.

摘要

目的

本研究旨在探讨（1）铁死亡（一种铁依赖性细胞死亡）在结扎诱导的大鼠牙周炎中的时间模式，以及（2）铁死亡抑制剂铁抑素-1对该模型的影响。

背景

铁死亡可能与多种疾病有关。然而，铁死亡在牙周炎中的作用仍未完全明确。

方法

在第一个实验中，于第0、1、2、7和10天处死25只结扎诱导牙周炎的大鼠。获取牙龈组织，通过免疫印迹法测定肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β以及铁死亡生物标志物，包括溶质载体家族3成员2（SLC3A2）、溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（Gpx4）。使用微型计算机断层扫描（μCT）和组织学方法，评估牙周软硬组织病变，包括牙槽骨嵴水平、周围牙槽骨的骨质特征、牙周组织炎症和牙周组织丧失情况。在第二项研究中，将16只诱导牙周炎的大鼠根据铁抑素-1治疗进行分组。在结扎前1天，给大鼠腹腔注射溶剂或铁抑素-1（1.5mg/kg/天），并于第7天和第10天处死。同时检测牙龈蛋白变化和牙周组织损伤情况。

结果

在第一项研究中，自第1天起SLC3A2/SLC7A11和Gpx4降低；然而，TNF-α/IL-1β在第7天和第10天升高。此外，μCT/组织学显示有骨质吸收特征、牙龈组织炎症和牙周附着丧失。在第二项研究中，注射铁抑素-1的大鼠与注射溶剂的大鼠相比，SLC3A2/SLC7A11和Gpx4显著升高，但TNF-α/IL-1β降低。它们还表现出骨吸收减少、组织炎症减轻和附着丧失减少。