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安徽中医药大学 药学院 中药研究与开发安徽省重点实验室,合肥 230012
Received:27 April 2022,
Published Online:14 July 2022,
Published:20 January 2023
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朱利,吴鸿飞.铁死亡在动脉粥样硬化中的作用及中医药干预研究进展[J].中国实验方剂学杂志,2023,29(02):244-252.
ZHU Li,WU Hongfei.Effect of Ferroptosis on Atherosclerosis and Chinese Medicine Intervention: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(02):244-252.
朱利,吴鸿飞.铁死亡在动脉粥样硬化中的作用及中医药干预研究进展[J].中国实验方剂学杂志,2023,29(02):244-252. DOI: 10.13422/j.cnki.syfjx.20221406.
ZHU Li,WU Hongfei.Effect of Ferroptosis on Atherosclerosis and Chinese Medicine Intervention: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(02):244-252. DOI: 10.13422/j.cnki.syfjx.20221406.
动脉粥样硬化(As)是脂质沉积于血管壁引起的一种慢性血管疾病,以脂质代谢紊乱、氧化应激和炎症为主要特征,为冠心病、心力衰竭和中风等心脑血管疾病的病理基础。铁死亡是一种新型调节性细胞死亡方式,其本质为铁依赖性脂质过氧化物累积引起的细胞死亡,在形态学、生物化学和遗传学方面与其他类型的细胞死亡不同。铁死亡发病机制复杂,其机制主要与谷胱甘肽/谷胱甘肽过氧化酶4抗氧化系统活性、铁代谢、铁自噬、脂质过氧化程度等多个途径有关。铁死亡在As过程中起着重要作用,参与As血管内皮细胞损伤、巨噬细胞炎症、泡沫细胞形成及血管平滑肌细胞增殖迁移等多个病理过程,已成为As研究的新靶点。中医药是我国独有且富有价值的医学科学,具有深厚的理论沉淀和实践积累。研究表明中药复方、中药单体及活性成分可调控血管相关细胞铁死亡,对As的防治具有独特优势。该文主要对铁死亡在As各病理环节中的作用及相关中医药干预进行综述,旨在从铁死亡角度为中医药防治As提供新方向。
Atherosclerosis (As) is a chronic vascular disease caused by lipid deposition on the vascular wall and is characterized by lipid metabolism disorder,oxidative stress,and inflammation. It is the pathological basis of cardiovascular and cerebrovascular diseases such as coronary heart disease,heart failure,and stroke. Ferroptosis is a new type of cell death caused by iron-dependent lipid peroxidation,which is morphologically,biologically,and genetically distinct from other types of cell death. The pathogenesis of ferroptosis is complex and is mainly related to the activity of the glutathione/glutathione peroxidase 4 antioxidant system,iron metabolism,iron autophagy,lipid peroxidation,and other pathways. Ferroptosis plays an important role in the process of As and is involved in many pathological processes such as vascular endothelial cell injury,macrophage inflammation,foam cell formation,and vascular smooth muscle cell proliferation and migration. It has become a new target for As research. Traditional Chinese medicine (TCM) is a unique and valuable medical science in China,with profound theoretical and practical accumulation. Studies have shown that Chinese medicine compounds,Chinese medicine monomers,and active ingredients can regulate ferroptosis in vascular-related cells and have unique advantages in the prevention and treatment of As. This article mainly reviewed the role of ferroptosis in various pathological links of As and related Chinese medicine intervention,aiming to provide a new direction for the prevention and treatment of As by Chinese medicine from the perspective of ferroptosis.
CHYU K Y , DIMAYUGA P C , SHAH P K . Immunogenetics of atherosclerosis-link between lipids,immunity,and genes [J]. Curr Atheroscler Rep , 2020 , 22 ( 10 ): 53 .
LI J , CAO F , YIN H L , et al . Ferroptosis:Past,present and future [J]. Cell Death Dis , 2020 , 11 ( 2 ): 88 .
张静 , 赵外荣 , 施雯婷 , 等 . 铁死亡及其在心血管疾病中的作用 [J]. 国际心血管病杂志 , 2020 , 47 ( 6 ): 339 - 343 .
CHEN X , LI X , XU X , et al . Ferroptosis and cardiovascular disease:Role of free radical-induced lipid peroxidation [J]. Free Radic Res , 2021 , 55 ( 4 ): 405 - 415 .
苏文全 , 吴圣贤 , 杜雅薇 . 从“脉生痰核”论治动脉粥样硬化 [J]. 中医学报 , 2019 , 34 ( 8 ): 1617 - 1620 .
XU T , DING W , JI X , et al . Molecular mechanisms of ferroptosis and its role in cancer therapy [J]. J Cell Mol Med , 2019 , 23 ( 8 ): 4900 - 4912 .
徐文慧 , 李沧海 , 姜廷良 . 铁死亡通路与中药干预机制研究进展 [J]. 中国中药杂志 , 2018 , 43 ( 20 ): 4019 - 4026 .
XIE Y , HOU W , SONG X , et al . Ferroptosis:Process and function [J]. Cell Death Differ , 2016 , 23 ( 3 ): 369 - 379 .
CHEN X , LI J , KANG R , et al . Ferroptosis:Machinery and regulation [J]. Autophagy , 2021 , 17 ( 9 ): 2054 - 2081 .
KOPPULA P , ZHUANG L , GAN B . Cystine transporter SLC7A11/xCT in cancer:Ferroptosis,nutrient dependency,and cancer therapy [J]. Protein Cell , 2021 , 12 ( 8 ): 599 - 620 .
BAJIC V P , VAN NESTE C , OBRADOVIC M , et al . Glutathione "Redox Homeostasis" and its relation to cardiovascular disease [J]. Oxid Med Cell Longev , 2019 , 2019 : 5028181 .
LIU M R , ZHU W T , PEI D S . System Xc-:A key regulatory target of ferroptosis in cancer [J]. Invest New Drugs , 2021 , 39 ( 4 ): 1123 - 1131 .
LIU J , XIA X , HUANG P . xCT:A critical molecule that links cancer metabolism to redox signaling [J]. Mol Ther , 2020 , 28 ( 11 ): 2358 - 2366 .
URSINI F , MAIORINO M . Lipid peroxidation and ferroptosis:The role of GSH and GPx4 [J]. Free Radic Biol Med , 2020 , 152 : 175 - 185 .
YANG W S , SRIRAMARATNAM R , WELSCH M E , et al . Regulation of ferroptotic cancer cell death by GPX4 [J]. Cell , 2014 , 156 ( 1-2 ): 317 - 331 .
LIU D S , DUONG C P , HAUPT S , et al . Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation [J]. Nat Commun , 2017 , 8 : 14844 .
SUN X , OU Z , CHEN R , et al . Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells [J]. Hepatology , 2016 , 63 ( 1 ): 173 - 184 .
FORCINA G C , DIXON S J . GPX4 at the crossroads of lipid homeostasis and ferroptosis [J]. Proteomics , 2019 , 19 ( 18 ): e1800311 .
SUI X , ZHANG R , LIU S , et al . RSL3 drives ferroptosis through GPX4 inactivation and ROS production in colorectal cancer [J]. Front Pharmacol , 2018 , 9 : 1371 .
FRIEDMANN ANGELI J P , CONRAD M . Selenium and GPX4,a vital symbiosis [J]. Free Radic Biol Med , 2018 , 127 : 153 - 159 .
HAYANO M , YANG W S , CORN C K , et al . Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation [J]. Cell Death Differ , 2016 , 23 ( 2 ): 270 - 278 .
HAN C , LIU Y , DAI R , et al . Ferroptosis and its potential role in human diseases [J]. Front Pharmacol , 2020 , 11 : 239 .
PATEL M , RAMAVATARAM D V . Non transferrin bound iron:Nature,manifestations and analytical approaches for estimation [J]. Indian J Clin Biochem , 2012 , 27 ( 4 ): 322 - 332 .
SUN X , OU Z , XIE M , et al . HSPB1 as a novel regulator of ferroptotic cancer cell death [J]. Oncogene , 2015 , 34 ( 45 ): 5617 - 5625 .
徐寒莹 , 张艺缤 , 张冬梅 , 等 . 铁死亡机制与中医药干预脑卒中后神经细胞铁死亡的研究进展 [J]. 中国实验方剂学杂志 , 2022 , doi: 10.13422/j.cnki.syfjx.20221105 http://dx.doi.org/10.13422/j.cnki.syfjx.20221105
GALARIS D , BARBOUTI A , PANTOPOULOS K . Iron homeostasis and oxidative stress:An intimate relationship [J]. Biochim Biophys Acta Mol Cell Res , 2019 , 1866 ( 12 ): 118535 .
米海潮 , 史敏 , 崔芳 . 铁自噬与铁死亡及其相关疾病的研究 [J]. 中国生物化学与分子生物学报 , 2022 , doi: 10.13865/j.cnki.cjbmb.2022.01.1497 http://dx.doi.org/10.13865/j.cnki.cjbmb.2022.01.1497 .
GAO M , MONIAN P , PAN Q , et al . Ferroptosis is an autophagic cell death process [J]. Cell Res , 2016 , 26 ( 9 ): 1021 - 1032 .
PARK E , CHUNG S W . ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation [J]. Cell Death Dis , 2019 , 10 ( 11 ): 822 .
LIU J , KUANG F , KROEMER G , et al . Autophagy-dependent ferroptosis:Machinery and regulation [J]. Cell Chem Biol , 2020 , 27 ( 4 ): 420 - 435 .
HOU W , XIE Y , SONG X , et al . Autophagy promotes ferroptosis by degradation of ferritin [J]. Autophagy , 2016 , 12 ( 8 ): 1425 - 1428 .
TANG D , CHEN X , KANG R , et al . Ferroptosis:Molecular mechanisms and health implications [J]. Cell Res , 2021 , 31 ( 2 ): 107 - 125 .
CHEN Z , YAN Y , QI C , et al . The role of ferroptosis in cardiovascular disease and its therapeutic significance [J]. Front Cardiovasc Med , 2021 , 8 : 733229 .
CHENG J , FAN Y Q , LIU B H , et al . ACSL4 suppresses glioma cells proliferation via activating ferroptosis [J]. Oncol Rep , 2020 , 43 ( 1 ): 147 - 158 .
CHEN X , KANG R , KROEMER G , et al . Ferroptosis in infection,inflammation,and immunity [J]. J Exp Med , 2021 , 218 ( 6 ): e20210518 .
KAGAN V E , MAO G , QU F , et al . Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis [J]. Nat Chem Biol , 2017 , 13 ( 1 ): 81 - 90 .
STOCKWELL B R , JIANG X , GU W . Emerging mechanisms and disease relevance of ferroptosis [J]. Trends Cell Biol , 2020 , 30 ( 6 ): 478 - 490 .
BERSUKER K , HENDRICKS J M , LI Z , et al . The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis [J]. Nature , 2019 , 575 ( 7784 ): 688 - 692 .
KRAFT VAN , BEZJIAN CT , PFEIFFER S , et al . GTP Cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling [J]. ACS Cent Sci , 2020 , 6 ( 1 ): 41 - 53 .
BAI Y , MENG L , HAN L , et al . Lipid storage and lipophagy regulates ferroptosis [J]. Biochem Biophys Res Commun , 2019 , 508 ( 4 ): 997 - 1003 .
GIMBRONE M A JR , GARCÍA-CARDEÑA G . Endothelial cell dysfunction and the pathobiology of atherosclerosis [J]. Circ Res , 2016 , 118 ( 4 ): 620 - 636 .
BOSSEBOEUF E , RAIMONDI C . Signalling metabolic pathways and iron homeostasis in endothelial cells in health,atherosclerosis and Alzheimer's disease [J]. Cells , 2020 , 9 ( 9 ): 2055 .
MARQUES V B , NASCIMENTO T B , RIBEIRO R F , et al . Chronic iron overload in rats increases vascular reactivity by increasing oxidative stress and reducing nitric oxide bioavailability [J]. Life Sci , 2015 , 143 : 89 - 97 .
MARQUES V B , LEAL M A S , MAGESKI J G A , et al . Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice:Role of oxidative stress and endothelial dysfunction [J]. Life Sci , 2019 , 233 : 116702 .
VINCHI F , PORTO G , SIMMELBAUER A , et al . Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction [J]. Eur Heart J , 2020 , 41 ( 28 ): 2681 - 2695 .
BAI T , LI M , LIU Y , et al . Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell [J]. Free Radic Biol Med , 2020 , 160 : 92 - 102 .
LI N , WANG W , ZHOU H , et al . Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury [J]. Free Radic Biol Med , 2020 , 160 : 303 - 318 .
XU H , JIANG J , CHEN W , et al . Vascular macrophages in atherosclerosis [J]. J Immunol Res , 2019 , 2019 : 4354786 .
KRONER A , GREENHALGH A D , ZARRUK J G , et al . TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord [J]. Neuron , 2014 , 83 ( 5 ): 1098 - 1116 .
AGORO R , TALEB M , QUESNIAUX V F J , et al . Cell iron status influences macrophage polarization [J]. PLoS One , 2018 , 13 ( 5 ): e0196921 .
MALHOTRA R , WUNDERER F , BARNES H J , et al . Hepcidin deficiency protects against atherosclerosis [J]. Arterioscler Thromb Vasc Biol , 2019 , 39 ( 2 ): 178 - 187 .
MARCIL V , LAVOIE J C , EMONNOT L , et al . Analysis of the effects of iron and vitamin C co-supplementation on oxidative damage,antioxidant response and inflammation in THP-1 macrophages [J]. Clin Biochem , 2011 , 44 ( 10-11 ): 873 - 883 .
CHISTIAKOV D A , MELNICHENKO A A , MYASOEDOVA V A , et al . Mechanisms of foam cell formation in atherosclerosis [J]. J Mol Med (Berl) , 2017 , 95 ( 11 ): 1153 - 1165 .
ZHANG Z , ZHANG F , AN P , et al . Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses [J]. Blood , 2011 , 118 ( 7 ): 1912 - 1922 .
LI W , XU L H , FORSSELL C , et al . Overexpression of transferrin receptor and ferritin related to clinical symptoms and destabilization of human carotid plaques [J]. Exp Biol Med (Maywood) , 2008 , 233 ( 7 ): 818 - 826 .
SU G , YANG W , WANG S , et al . SIRT1-autophagy axis inhibits excess iron-induced ferroptosis of foam cells and subsequently increases IL-1Β and IL-18 [J]. Biochem Biophys Res Commun , 2021 , 561 : 33 - 39 .
PENG Q , LIU H , LUO Z , et al . Effect of autophagy on ferroptosis in foam cells via Nrf2 [J]. Mol Cell Biochem , 2022 , 477 ( 5 ): 1597 - 1606 .
LIU Y X , YUAN P Z , WU J H , et al . Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis [J]. J Mol Med (Berl) , 2021 , 99 ( 11 ): 1511 - 1526 .
SAMPILVANJIL A , KARASAWA T , YAMADA N , et al . Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells [J]. Am J Physiol Heart Circ Physiol , 2020 , 318 ( 3 ): H508 - H518 .
YANG Z , SHI J , CHEN L , et al . Role of pyroptosis and ferroptosis in the progression of atherosclerotic plaques [J]. Front Cell Dev Biol , 2022 , 10 : 811196 .
RAMAKRISHNAN L , PEDERSEN S L , TOE Q K , et al . The Hepcidin/Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells [J]. Sci Rep , 2018 , 8 ( 1 ): 12972 .
MA W Q , SUN X J , ZHU Y , et al . Metformin attenuates hyperlipidaemia-associated vascular calcification through anti-ferroptotic effects [J]. Free Radic Biol Med , 2021 , 165 : 229 - 242 .
何信用 , 王俊岩 , 宋囡 , 等 . 二陈汤合桃红四物汤调控p53/SLC7A11介导的氧化损伤及铁死亡抗动脉粥样硬化的作用及机制研究 [J]. 中华中医药杂志 , 2020 , 35 ( 5 ): 2344 - 2348 .
王杰 , 贾连群 , 宋囡 , 等 . 四君子汤通过铁死亡途径改善动脉粥样硬化小鼠肝脏脂质沉积 [J]. 解剖科学进展 , 2021 , 27 ( 1 ): 75 - 78 .
杨雪 , 周飞 , 杨炀 , 等 . 葛根素联合丹参酮Ⅱ A 对糖尿病血管病变大鼠t-PA,PAI-1及氧化应激的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 19 ): 46 - 54 .
吴瑶 , 宋囡 , 贾连群 , 等 . 丹参酮Ⅱ A 对ApoE -/- 小鼠肝脏脂质沉积及铁死亡相关蛋白表达的影响 [J]. 中国病理生理杂志 , 2020 , 36 ( 7 ): 1261 - 1268 .
黄紫霞 , 吴明月 , 许峰 , 等 . 柴胡皂苷A通过抑制氧化应激和铁死亡减轻过氧化氢诱导的人脐静脉内皮细胞损伤 [J]. 中国动脉硬化杂志 , 2022 , 30 ( 1 ): 43 - 48 .
郑芳 , 巩红岩 , 秦元旭 , 等 . 姜黄素预处理对体外循环大鼠心肌缺血再灌注损伤的保护与抗氧化作用 [J]. 中国实验方剂学杂志 , 2012 , 18 ( 5 ): 148 - 151 .
LIN X , BAI D , WEI Z , et al . Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway [J]. PLoS One , 2019 , 14 ( 5 ): e0216711 .
SHENG S , XU J , LIANG Q , et al . Astragaloside Ⅳ inhibits bleomycin-induced ferroptosis in human umbilical vein endothelial cells by mediating LPC [J]. Oxid Med Cell Longev , 2021 , 2021 : 6241242 .
李敏 , 张丹 , 张林 , 等 . 银杏花化学成分对血管内皮细胞铁死亡的抑制作用 [J]. 国际药学研究杂志 , 2020 , 47 ( 10 ): 857 - 862 .
时召平 , 周晓慧 , 徐倩 , 等 . 丹皮酚对大鼠急性心肌梗死所致心肌纤维化的影响及机制 [J]. 中国实验方剂学杂志 , 2015 , 21 ( 9 ): 150 - 155 .
JIN Z L , GAO W Y , LIAO S J , et al . Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis [J]. ASN Neuro , 2021 , 13 : 17590914211010647 .
何海 , 黄翰文 , 施晓艳 , 等 . 丹皮酚调控ApoE -/- 小鼠胆汁酸代谢发挥抗动脉粥样硬化作用 [J]. 中国动脉硬化杂志 , 2021 , 29 ( 2 ): 123 - 128,165 .
WU H , SONG A , HU W , et al . The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK/mTOR signaling pathway [J]. Front Pharmacol , 2018 , 8 : 948 .
LIU Y R , CHEN J J , DAI M . Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF- α release [J]. Acta Pharmacol Sin , 2014 , 35 ( 4 ): 483 - 488 .
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