摘要
目的探讨香菇多糖(lentinan,LNT)对亚砷酸钠(sodium arsenite,SA)染毒小鼠肝组织铁死亡的干预效应与机制。方法C57BL/6N雄性小鼠经SA低剂量、高剂量染毒,以及LNT干预SA高剂量染毒后,苏木精-伊红(HE)染色评价肝组织病理损伤;酶联免疫吸附法或免疫蛋白印迹法检测肝组织肿瘤坏死因子α(tumor necrosis factorα,TNFα)、白细胞介素6(interleukin-6,IL-6)、铁自噬或铁死亡标志物含量或表达。结果与对照组相比,SA染毒诱导小鼠肝组织TNFα和IL-6水平升高,铁自噬标志物铁蛋白重链(ferritin heavy chain 1,FTH1)和微管相关蛋白1轻链3B(microtubule associated protein 1 light chain 3B,MAP1LC3B)含量升高,铁死亡标志物谷胱甘肽过氧化酶4(glutathione peroxidase 4,GPX4)水平下调(P<0.05);与SA高剂量组相比,LNT干预后显示肝组织病理损伤减轻,TNFα、IL-6、FTH1和MAP1LC3B水平下调,而GPX4水平上调(P<0.05);免疫蛋白印迹实验显示,LNT干预拮抗SA高剂量组FTH1、自噬标记蛋白LC3B/A水平升高或拮抗FTH1与LC3B或泛素(ubiquitin,Ub)共表达(P<0.05)。结论LNT拮抗SA染毒小鼠肝组织病理损伤和铁死亡,可能与TNFα-铁自噬信号抑制有关。
Objective To explore the effect and mechanism of lentinan(LNT)on hepatic tissue ferroptosis in mice exposed to sodium arsenite(SA).Methods C57BL/6N male mice were exposed to SA low-dose,SA high-dose,and LNT intervention combined with SA high-dose,then,hematoxylin and eosin(HE)staining was applied to assess pathological liver tissue damage;Enzyme-linked immunosorbent and Western blot were used to detect the content or expression of tumor necrosis factorα(TNFα),interleukin-6(IL-6),ferritinophagy or ferroptosis biomarkers.Results Compared with the control group,SA exposure induced the elevated levels of TNFα,IL-6,ferritinophagy biomarker ferritin heavy chain 1(FTH1)and microtubule-associated protein 1 light chain 3B(MAP1LC3B)in mice liver tissue,while levels the ferroptosis biomarker GPX4 decreased(P<0.05).Compared with SA high-dose groups,LNT intervention showed the reduced pathological liver damage and the downregulated levels of TNFα,IL-6,FTH1,and MAP1LC3B,while the level of GPX4 upregulated(P<0.05).Western blot experiment showed that LNT intervention antagonized the upregulated levels of FTH1,and autophagy biomarker LC3B/A,and antagonized the increased co-expressions of FTH1 with LC3B or Ub protein in SA high-dose group(P<0.05).Conclusions LNT antagonizes SA-exposed hepatic pathological injury and ferroptosis in mice,possibly associated with inhibition of TNFα-ferritinophagy signaling.
作者
杨渊
鲍家成
邓业康
陈秧
何琴
YANG Yuan;BAO Jiacheng;DENG Yekang;CHEN Yang;HE Qin(Guangxi Key Laboratory of Environmental Exposure Omics and Whole Life Cycle Health,School of Public Health,Guilin Medical College,Guilin 541199,China;Hunan Key Laboratory of Dong Medicine Research,ResearchCenter of Ethnic Medicine,Hunan Medical University,Huaihua 418000)
出处
《中国比较医学杂志》
北大核心
2025年第1期41-48,共8页
Chinese Journal of Comparative Medicine
基金
广西自然科学基金(2023JJA140042)
湖南省自然科学基金(2021JJ30484,2022JJ30426)
广西大学生创新训练项目(202410601041)。
关键词
亚砷酸钠
肝毒性
铁死亡
香菇多糖
铁自噬
sodium arsenite
hepatotoxicity
ferroptosis
lentinan
ferritinophagy
