Zhao Mengxue, Wang Hongqian, Zhang Yumeng, Lv Chuang, Guan Jing, Chen Xi
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Anhui Provincial Key Laboratory of Digestive Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
J Gastroenterol Hepatol. 2024 Dec;39(12):2709-2722. doi: 10.1111/jgh.16738. Epub 2024 Sep 16.
Selenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.
Serum selenium level and ferroptosis-related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS-treated Caco-2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4, ferroptosis-related genes, were detected in Caco-2 cells and mouse intestines.
Serum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The in vivo experiments showed that selenium treatment ameliorated DSS-induced colitis and inhibited ferroptosis in IECs. The in vitro results suggested that selenium supplementation inhibited DSS-induced ferroptosis in Caco-2 cells. GPX4 was upregulated after selenium supplementation both in vivo and in vitro.
Serum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS-induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4.
硒是人体必需的微量营养素，已被证明对溃疡性结肠炎（UC）具有保护作用，但其确切机制尚不清楚。本研究旨在探讨硒在结肠炎中对肠道上皮细胞（IECs）铁死亡的保护作用。
检测UC患者和健康对照者血清硒水平及结肠黏膜中铁死亡相关基因的表达。在葡聚糖硫酸钠（DSS）处理的小鼠中研究亚硒酸钠补充对实验性结肠炎的影响。通过评估DSS处理的Caco-2细胞的细胞死亡率、细胞内亚铁含量、脂质活性氧水平和线粒体膜损伤，评价亚硒酸钠对IEC铁死亡的影响。此外，在Caco-2细胞和小鼠肠道中检测铁死亡相关基因谷胱甘肽过氧化物酶4（GPX4）和酰基辅酶A合成酶长链家族成员4。
与健康个体相比，UC患者血清硒水平降低。此外，血清硒水平与疾病活动度呈负相关，并与临床炎症和营养指标相关。UC黏膜中GPX4的表达与血清硒水平呈正相关。体内实验表明，硒治疗可改善DSS诱导的结肠炎并抑制IECs中的铁死亡。体外实验结果表明，补充硒可抑制DSS诱导的Caco-2细胞铁死亡。体内和体外补充硒后GPX4均上调。
UC患者血清硒水平与IEC铁死亡有关。补充硒通过上调GPX4的表达减轻DSS诱导的结肠炎并抑制IECs中的铁死亡。
