摘要
目的通过益糖康对db/db小鼠胰岛β细胞线粒体转铁通路的调节作用,探讨其对抗铁死亡,改善胰岛功能的机制。方法该研究应用2型糖尿病(type 2 diabetes mellitus,T2DM)动物模型db/db小鼠,通过在体实验进行分组,在整体水平测量不同条件下动物的空腹血糖,在组织水平观察胰腺组织、胰岛β细胞的状态改变及胰岛素分泌功能,在分子水平阐明胰岛β细胞线粒体相关铁死亡机制。结果模型组小鼠胰岛功能明显降低,西药对照组(利拉鲁肽)及益糖康高剂量组胰岛功能改善明显;在形态学上,HE染色发现模型组小鼠胰岛细胞排列紊乱,胞质欠丰富,西药对照组及益糖康高剂量组此情况改善较为明显;免疫组化法检测胰岛素分泌情况,发现模型组胰岛素分泌明显减少,西药对照组及益糖康高剂量组胰岛素分泌明显增加,透射电镜观察发现模型组小鼠胰岛β细胞线粒体明显变小,膜增厚,嵴减少,用药后此情况得以改善,益糖康高剂量组改善最为明显;在分子水平上,模型组线粒体转铁通路蛋白MFRN2、NFS1、ABCB7及铁死亡蛋白SLC7A11的基因表达及蛋白表达均明显降低,西药对照组及益糖康高剂量组基因及蛋白的表达明显改善。结论T2DM影响胰岛β细胞线粒体转铁通路功能,导致线粒体及细胞内铁代谢障碍,引起细胞脂质过氧化发生铁死亡,益糖康可通过改善线粒体MFRN2/NFS1/ABCB7转铁通路功能发挥对抗铁死亡的作用,进而改善胰岛功能。
Objective To investigate the regulatory effect of Yitangkang(益糖康)on the mitochondrial iron transfer pathway in pancreatic beta cells of db/db mice,and its mechanism of combating iron death and improving pancreatic function.Methods This study used type 2 diabetes mellitus(T2DM)animal model db/db mice and divided them into groups through in vivo experiments.The general state of the animals under different conditions was observed at the overall level,and the state changes and insulin secretion function of pancreatic tissue and pancreatic beta cells were observed at the tissue level.The molecular level elucidated the mechanism of mitochondrial related ferroptosis in pancreatic beta cells.Results The pancreatic function of model group mice was significantly reduced,while the Western medicine control group(Liraglutide)and Yitangkang high-dose group showed significant improvement in pancreatic function;Morphologically,HE staining revealed disordered arrangement of pancreatic islet cells and insufficient cytoplasm in model group mice,with significant improvement observed in the Western medicine control group and Yitangkang highdose group;Immunohistochemical staining was used to detect insulin secretion,and it was found that insulin secretion was significantly reduced in the model group,while insulin secretion was significantly increased in the Western medicine control group and Yitangkang high-dose group.Transmission electron microscopy observation showed that the mitochondria of pancreatic beta cells in model group mice were significantly reduced,the membrane thickened,and the cristae decreased.After medication,this situation was improved,and the improvement was most significant in the Yitangkang high-dose group;At the molecular level,the gene and protein expression of mitochondrial transferrin pathway proteins MFRN2,NFS1,ABCB7,and ferroptosis protein SLC7A11 were significantly reduced in the model group,while the gene and protein expression were significantly improved in the Western medicine control group and Yitangkang highdose group.Conclusion T2DM affects the mitochondrial iron transfer pathway function of pancreatic beta cells,leading to mitochondrial and intracellular iron metabolism disorders,causing cell lipid peroxidation and iron death.Yitangkang can improve the mitochondrial MFRN2/NFS1/ABCB7 iron transfer pathway function,exert an anti iron death effect,and thus improve pancreatic function.
作者
张栏译
沈子涵
苏嘉楠
孙贵炎
单德红
杨宇峰
石岩
ZHANG Lanyi;SHEN Zihan;SU Jianan;SUN Guiyan;SHAN Dehong;YANG Yufeng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)
出处
《辽宁中医药大学学报》
2025年第8期18-22,F0003,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家重点基础研究发展计划(973计划)项目(2013CB532004-01)
辽宁省中央引导地方科技发展专项(2019JH6/10200009)
辽宁省“兴辽英才计划”项目(XLYC2008027)
辽宁省“百千万人才工程”项目(2020921039)
辽宁中医药大学中西医结合学院“岐济”人才支撑计划项目(结合字〔2022〕15号)。
关键词
2型糖尿病
胰岛Β细胞
线粒体转铁通路
铁死亡
益糖康
type 2 diabetes mellitus
pancreatic beta cells
mitochondrial iron transfer pathway
ferroptosis
Yitangkang(益糖康)
