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铁死亡关键信号通路在脑缺血中的作用机制及其中药防治研究. (2025). 环球医学研究, 2(3), 39-44. https://doi.org/10.62836/medicine.v2i3.850
Copyright (c) 2025 汤杨熠
This work is licensed under a Creative Commons Attribution 4.0 International License.
铁死亡关键信号通路在脑缺血中的作用机制及其中药防治研究
汤杨熠
浙江中医药大学，浙江杭州
摘要：在我国，脑缺血是导致成年人死亡、残疾的首位病因。脑缺血涉及多个病理机制，如氧化应激、炎症反应、铁死亡等。其中铁死亡是一种铁依赖性的程序性细胞死亡方式，与缺血性脑损伤密切相关， 通过铁代谢障碍、脂质过氧化多种途径参与脑缺血的发生发展。近年来，对铁死亡的研究中发现中药可利用铁死亡相关的信号通路来改善铁代谢，减轻脑缺血损伤，保护神经细胞。中药治疗具有多靶点、多通路、多层次、不良反应少的特点，已成为当前研究脑缺血治疗的新兴热点。
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[31] 赵冯岩,杨浩澜,朱炎贞,等.基于网络药理学从铁死亡途径研究补阳还五汤调控缺血性脑卒中的作用机制[J].湖南中医药大学学报.2021,41(07):1065-72.
[32] 向军军,李丽琴,李建铮,等.基于铁死亡探讨温阳复元方对脑缺血再灌注损伤大鼠神经损伤的保护机制[J].中药新药与临床药理.2023,34(12):1649-57.
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[2] SUN S, CHEN X, GAO Y, et al. Mn-SOD Upregulation by Electroacupuncture Attenuates Ischemic Oxidative Damage via CB1R-Mediated STAT3 Phosphorylation [J]. Molecular Neurobiology, 2016, 53(1): 331-43.
[3] GAO L, JIANG T, GUO J, et al. Inhibition of Autophagy Contributes to Ischemic Postconditioning-Induced Neuroprotection against Focal Cerebral Ischemia in Rats [J]. Plos One, 2012, 7(9): e46092.
[4] ANGELI J F, SHAH R, RATT DA, et al. Ferroptosis Inhibition: Mechanisms and Opportunities [J]. Trends in Pharmacological Sciences, 2017, 38(5): 489-98.
[5] BOGDAN AR, MIYAZAWA M, HASHIMOTO K, et al. Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death and Disease [J]. Trends Biochem Sci, 2016, 41(3): 274-86.
[6] LI J, CAO F, YIN HL, et al. Ferroptosis: past, present and future [J]. Cell Death Dis, 2020, 11(2): 88.
[7] TUO QZ, LEI P, JACKMAN KA, et al. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke [J]. Mol Psychiatry, 2017, 22(11): 1520-30.
[8] SHE X, LAN B, TIAN H, et al. Cross Talk Between Ferroptosis and Cerebral Ischemia [J]. Front Neurosci, 2020, 14: 776.
[9] LIU X. Changes and significance of serum CXCL-16, GDF- 15, PLA-2 levels in patients with cerebral infarction [J]. Am J Transl Res, 2021, 13(5): 5617-22.
[10] TUO QZ, LIU Y, XIANG Z, et al. Thrombin induces ACSL4- dependent ferroptosis during cerebral ischemia/reperfusion [J]. Signal Transduct Target Ther,2022, 7(1): 59.
[11] MURALIKRISHNA ADIBHATLA R, HATCHER JF. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia [J]. Free Radical Biology and Medicine, 2006, 40(3): 376-87.
[12] DIXON SJ, LEMBERG KM, LAM RECHT MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell, 2012, 149(5): 1060-72.
[13] HSIEH C H, LIN YJ, CHEN WL, et al. HIF- 1α triggers long- lasting glutamate excitotoxicity via system x(c)(-) in cerebral ischaemia-reperfusion [J]. J Pathol,2017, 241(3): 337-49.
[14] LEWERENZ J, HEWETT SJ, HUANG Y, et al. The cystine/ glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities [J]. Antioxid Redox Signal, 2013, 18(5): 522-55.
[15] SHI B, MA M, ZHENG Y, et al. mTOR and Beclin1: Two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury [J]. Cell Physiol, 2019, 234(8): 12562-8.
[16] 叶宇恒,钱玲玲,王如兴,等.心肌缺血再灌注损伤中铁死亡的调控机制研究进展[J].心血管病学进展.2023,44(05):416-9.
[17] LI C, WU Z, XUE H, et al. Ferroptosis contributes to hypoxic- ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway [J].CNS Neurosci Ther, 2022, 28(12): 2268-80.
[18] LIU Y, GU W. p53 in ferroptosis regulation: the new weapon for the old guardian [J]. Cell Death and Differentation, 2022, 29(5): 895-910.
[19] 王成毅,蔡粤芳,宁振求,等.壮通饮通过Nrf2-SCL7A11/xCT-Gpx4通路调控铁死亡改善脑缺血再灌注损伤[J].中山大学学报(医学科学版),2024,45(4):539-48.
[20] XU R, WANG W, ZHANG W. Ferroptosis and the bidirectional regulatory factor p53 [J]. Cell Death Discov, 2023, 9(1): 197.
[21] SU H, PENG C, LIU Y. Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer [J]. Front Cell Dev Biol, 2024, 12: 1372330.
[22] KILIC-EREN M, BOYLU T, TABOR V. Targeting PI3K/Akt represses Hypoxia inducible factor- 1α activation and sensitizes Rhabdomyosarcoma and Ewing’s sarcoma cells for apoptosis [J]. Cancer Cell Int, 2013, 13: 36.
[23] LI M, LI J, WU H, et al. Baicalein ameliorates cerebral ischemia- reperfusion injury by inhibiting ferroptosis via regulating GPX4/ACSL4/ACSL3 axis [J]. Chemico-Biological Interactions, 2022, 366: 110137.
[24] 余松祚.黄酮类中药干预程序性细胞死亡在缓解脑缺血再灌注损伤中的研究进展[J].医学信息.2023,36(02):171-5.
[25] GAO J, MA C, XIA D, et al. Icariside II preconditioning evokes robust neuroprotection against ischaemic stroke, by targeting Nrf2 and the OXPHOS/NF-κB/ferroptosis pathway [J]. British Journal of Pharmacology, 2023, 180(3): 308-29.
[26] WANG L, LIU C, WANG L, et al. Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62/Keap1/ Nrf2 pathway-mediated ferroptosis [J]. European Journal of Pharmacology, 2023, 944: 175516.
[27] WANG LL, LIU WP ,TANG B, et al. Panax notoginseng saponins attenuate cerebral ischemia reperfusion injury in rats by inhibiting ferroptosis and inflammation [J]. Chinese Journal of Immunology, 2022, 03: 296-300.
[28] GE L, ZHANG J, XU M, et al. Effect of tetramethylpyrazine on oxidative stress,Ca2+-AT activity and inflammatory factors after cerebral ischemia/reperfusion injury in rats [J]. International Journal of Laboratory Medicine, 2021, 05: 517-520.
[29] GAN CC, WANG QME, CHEN G, et al. Study of the Protective Effect of Tetrahydropalmatine on the Injury of Suckling Rat Hippocampal Neurons due to Hypoxia and Sugar Deficiency [J]. Chinese Journal of Ethnomedicine and Ethnopharmacy, 2019, 19: 14-18.
[30] 蔡国英,刘均广,叶佳蓓,等.补阳还五汤增强GPX4表达抑制铁死亡减轻脑缺血再灌注损伤[J].承德医学院学报.2024,41(01):10-4.
[31] 赵冯岩,杨浩澜,朱炎贞,等.基于网络药理学从铁死亡途径研究补阳还五汤调控缺血性脑卒中的作用机制[J].湖南中医药大学学报.2021,41(07):1065-72.
[32] 向军军,李丽琴,李建铮,等.基于铁死亡探讨温阳复元方对脑缺血再灌注损伤大鼠神经损伤的保护机制[J].中药新药与临床药理.2023,34(12):1649-57.
[33] 邓秋媚,吴林,袁莉,等.温阳复元方通过调控miRNA-137/线粒体铁死亡通路保护大鼠脑缺血再灌注损伤机制研究[J]. 辽宁中医药大学学报.2024,26(02):31-6.
[34] 郭荷娜,康蓓,赵婧钰,等.丹红注射液对脑缺血再灌注损伤大鼠皮质区新生微血管的影响研究[J].实用心脑肺血管病杂志.2020,28(02):69-73.
[35] 柳挺.丹红注射液对小鼠脑缺血再灌注损伤的保护作用[J]. 中医临床研究.2018,10(23):5-6.