肉桂醛缓解高糖诱导的SH-SY5Y细胞铁死亡的作用研究  

Cinnamaldehyde Alleviates High Glucose-Induced Ferroptosis in SH-SY5Y Cells

作　　者：陈秀婷 杨莹莹 王佳琪 周金玲 夏星[2] CHEN Xiuting;YANG Yingying;WANG Jiaqi;ZHOU Jinling;XIA Xing(School of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200;Key Laboratory of TCM Neuro-metabolism and Immunopharmacology of Guangxi Education Department,Guangxi University of Chinese Medicine,Nanning 530200)

机构地区：[1]广西中医药大学药学院,南宁530200 [2]广西中医药大学广西高校中药神经-代谢及免疫药理重点实验室,南宁530200

出　　处：《中药药理与临床》2025年第2期54-59,79,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81960728);广西高校中青年教师科研基础能力提升项目(编号:2022KY0302);广西中医药大学博士科研启动基金项目(编号:2021BS007);广西中医药大学桂派杏林拔尖人才项目(编号:2022C007);广西中医药大学桂派中医药传承创新团队项目(编号:2022B005);广西中医药大学研究生教育创新计划项目(编号:YCSZ2022006);广西中医药大学青年创新研究团队项目(编号:2015QT002)。

摘　　要：目的:探讨肉桂醛对糖尿病相关神经细胞铁死亡的保护作用。方法:以高糖引发分化成熟的SH-SY5Y神经细胞损伤,分别以肉桂醛13.2、26.4 mmol/L、利普司他汀-1 0.01 mmol/L作用于细胞。用MTT法检测细胞活力;荧光显微镜观察细胞脂质活性氧(ROS)水平;流式细胞术检测细胞内Fe^(2+)水平、线粒体膜电位变化;透射电镜观察细胞线粒体形态变化;Western blot法检测转铁蛋白(TFRC)、铁蛋白重链(FTH1)、轻链亚基溶质载体家族7成员11(SLC7A11)蛋白的表达。结果:高糖导致分化的SH-SY5Y细胞活力较正常细胞显著降低,细胞内脂质ROS水平增加,线粒体膜电位及GSH/GSSG比值降低,Fe^(2+)水平显著增加及铁死亡负调控蛋白显著降低(P<0.01);肉桂醛的处理使受损的细胞活力明显增加(P<0.05),细胞内脂质ROS水平显著降低(P<0.01),线粒体膜电位显著升高及GSH/GSSG比值明显升高(P<0.05或P<0.01),异常的Fe^(2+)水平明显降低(P<0.05),明显改善了高糖引起的细胞线粒体萎缩、脊断裂、消失等畸变现象,显著上调铁死亡负调节蛋白FTH1、SLC7A11蛋白的表达,显著下调TFRC蛋白的表达(P<0.01)。结论:肉桂醛可缓解高糖导致的细胞铁死亡,其机制可能在于调节铁代谢,抑制细胞的铁依赖性脂质过氧化损伤。Objective:To investigate the protective effect of cinnamaldehyde on diabetes-related ferroptosis in neurocytes.Methods:The injury of mature SH-SY5Y neuronal cells was triggered by high glucose,and then the cells were treated with cinnamaldehyde(13.2 and 26.4 mmol/L)and lipstatin-1(0.01 mmol/L),respectively.The cell viability was determined by the MTT assay,and the reactive oxygen species(ROS)level in cells was observed by fluorescence microscopy.Flow cytometry was employed to determine the intracellular Fe^(2+)level and mitochon-drial membrane potential(MMP).The morphological changes of mitochondria were observed by transmission electron microscopy.The pro-tein levels of transferrin receptor(TFRC),ferritin heavy chain 1(FTH1),and solute carrier family 7 member 11(SLC7A11)were deter-mined by Western blotting.Results:Compared with normal cells,the SH-SY5Y cells exposed to high glucose showed decreased viability,in-creased intracellular ROS level,decreased MMP and glutathione(GSH)/oxidized glutathione(GSSG)ratio,elevated Fe^(2+)level,and downreg-ulated expression levels of negative regulatory proteins of ferroptosis.Compared with the cells exposed to high glucose,cinnamaldehyde treat-ment improved the cell viability(P<0.05),lowered the intracellular ROS level(P<0.01),increased the MMP and GSH/GSSG ratio(P<0.05 or P<0.01),and lowered the Fe^(2+)level(P<0.05).In addition,cinnamaldehyde ameliorated high glucose-induced aberrations such as mitochondrial atrophy and breakage and disappearance of mitochondrial cristae,upregulated the expression levels of FTH1 and SLC7A11(negative regulators of ferroptosis),and downregulated the protein level of TFRC(P<0.01).Conclusion:Cinnamaldehyde alleviates high glucose-induced ferroptosis by modulating the iron metabolism and inhibiting cellular iron-dependent lipid peroxidation.

关 键 词：肉桂醛 神经损伤 高糖 铁死亡 转铁蛋白 铁蛋白重链 轻链亚基溶质载体家族7成员11 线粒体 谷胱甘肽 谷胱甘肽过氧化酶 

分 类 号：R285[医药卫生—中药学]