甘肃中医药大学,兰州 730000
张钦媛,在读博士,从事内分泌及代谢病的中医药防治研究,E-mail:xlyxnew2022@sina.com
金智生,硕士,博士生导师,从事内分泌及代谢病的中医药防治研究,E-mail:jzsgszy@126.com
收稿:2023-04-23,
网络出版:2023-06-16,
纸质出版:2024-03-20
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张钦媛,金智生,姜晓雪等.铁死亡对糖尿病及其并发症影响及中药干预进展[J].中国实验方剂学杂志,2024,30(06):280-288.
ZHANG Qinyuan,JIN Zhisheng,JIANG Xiaoxue,et al.Effect of Ferroptosis on Diabetes Mellitus and Its Complications and Intervention of Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):280-288.
张钦媛,金智生,姜晓雪等.铁死亡对糖尿病及其并发症影响及中药干预进展[J].中国实验方剂学杂志,2024,30(06):280-288. DOI: 10.13422/j.cnki.syfjx.20231109.
ZHANG Qinyuan,JIN Zhisheng,JIANG Xiaoxue,et al.Effect of Ferroptosis on Diabetes Mellitus and Its Complications and Intervention of Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):280-288. DOI: 10.13422/j.cnki.syfjx.20231109.
糖尿病是由于胰岛素分泌绝对或相对不足引起的以长期高血糖症为特征的一种代谢性疾病。随着糖尿病病情的进展,罹患糖尿病肾病、糖尿病心肌病、糖尿病合并非酒精性脂肪肝病等并发症的人数不断扩增,给患者及社会都带来沉重负担。铁死亡是近年来广受关注的一种细胞新型程序性死亡方式,主要是指在铁离子过载下,脂质过氧化物过度累积导致的细胞死亡。现已有多项研究发现糖尿病及其并发症中存在铁死亡现象,通过抑制铁死亡可极大减缓糖尿病及其并发症的发生和进展。中药是我国独具特色的瑰宝,具有多通路、多方向的优势且价廉、不良反应小的特色,已被广泛用于糖尿病及其并发症的治疗并取得较好疗效,为广大患者带来福音。从中药调节铁死亡的角度入手可能是未来治疗糖尿病及其并发症的新方向。该文简要阐述铁死亡机制,探讨铁死亡与糖尿病及其并发症之间联系,总结中药干预铁死亡治疗糖尿病及其并发症的研究现状,并提出建议,以期为中药治疗糖尿病及其并发症的深入研究提供参考依据。
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by absolute or relative insufficiency of insulin secretion. As the disease progresses, patients begin to suffer from diabetic nephropathy, diabetic cardiomyopathy, non-alcoholic fatty liver disease or other complications, which increase the burden on the patients. Moreover, the number of patients is increasing, which brings a heavy burden to the society. Ferroptosis is a new type of programmed cell death which has attracted wide attention in recent years. It refers to the cell death caused by the excessive accumulation of lipid peroxide under the overload of iron ions. Studies have discovered that ferroptosis exists in diabetes mellitus and its complications. Inhibiting ferroptosis can greatly slow down the occurrence and progression of diabetes mellitus and its complications. Chinese medicine, the unique medical treasure in China, acts in a multi-pathway, multi-target manner and is praised for the cheap price, low toxicity, and mild side effects. It has been widely used in the treatment of diabetes mellitus and its complications and has demonstrated definite therapeutic effects, bringing the good news for the majority of patients. The regulation of ferroptosis by Chinese medicine may be a new direction for the treatment of diabetes mellitus and its complications in the future. This paper briefly describes the mechanism of ferroptosis, explores the relationship of ferroptosis with diabetes mellitus and its complications, summarizes the research status of Chinese medicine interventions, and puts forward suggestions, aiming to provide a reference for further research on the treatment of diabetes mellitus and its complications with Chinese medicine.
SUN H , SAEEDI P , KARURANGA S , et al . Erratum to "IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 "[J]. Diabetes Res Clin Pract , 2023 , 204 : 110945 .
DIXON S J , LEMBERG K M , LAMPRECHT M R , et al . Ferroptosis:An iron-dependent form of nonapoptotic cell death [J]. Cell , 2012 , 149 ( 5 ): 1060 - 1072 .
王笑冉 , 赵文霞 , 苗明三 . 铁死亡对器官纤维化的影响及中药干预进展 [J]. 中国实验方剂学杂志 , 2023 , 29 ( 8 ): 246 - 256 .
LI J , CAO F , YIN H L , et al . Ferroptosis:Past, present and future [J]. Cell Death Dis , 2020 , 11 ( 2 ): 88 .
KOPPULA P , ZHANG Y , ZHUANG L , et al . Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer [J]. Cancer Commun (Lond) , 2018 , 38 ( 1 ): 12 .
BAYıR H , ANTHONYMUTHU T S , TYURINA Y Y , et al . Achieving life through death: Redox biology of lipid peroxidation in ferroptosis [J]. Cell Chem Biol , 2020 , 27 ( 4 ): 387 - 408 .
LI C , DENG X , XIE X , et al . Activation of glutathione peroxidase 4 as a novel anti-inflammatory strategy [J]. Front Pharmacol , 2018 , 9 : 1120 .
MAGTANONG L , KO P J , TO M , et al . Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state [J]. Cell Chem Biol , 2019 , 26 ( 3 ): 420 - 432.e9 .
FRIEDMANN ANGELI J P , CONRAD M . Selenium and GPX4, a vital symbiosis [J]. Free Radic Biol Med , 2018 , 127 : 153 - 159 .
LIN W , WANG C , LIU G , et al . SLC7A11/xCT in cancer:Biological functions and therapeutic implications [J]. Am J Cancer Res , 2020 , 10 ( 10 ): 3106 - 3126 .
程峰 , 张庸 , 王祥 , 等 . 谷胱甘肽过氧化物酶GPX4在铁死亡中的作用与机制研究进展 [J]. 现代肿瘤医学 , 2021 , 29 ( 7 ): 1254 - 1258 .
JARAMILLO M C , ZHANG D D . The emerging role of the Nrf2-Keap1 signaling pathway in cancer [J]. Genes Dev , 2013 , 27 ( 20 ): 2179 - 2191 .
FAN Z , WIRTH A K , CHEN D , et al . Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis [J]. Oncogenesis , 2017 , 6 ( 8 ): e371 .
LI D , LIU X , PI W , et al . Fisetin attenuates doxorubicin-induced cardiomyopathy in vivo and in vitro by inhibiting ferroptosis through SIRT1/Nrf2 signaling pathway activation [J]. Front Pharmacol , 2021 , 12 : 808480 .
CHENG H , WANG P , WANG N , et al . Neuroprotection of Nrf2 against ferroptosis after traumatic brain injury in mice [J]. Antioxidants (Basel) , 2023 , 12 ( 3 ): 125 .
ZENG F , LAN Y , WANG N , et al . Ferroptosis: A new therapeutic target for bladder cancer [J]. Front Pharmacol , 2022 , 13 : 1043283 .
张启立 , 赵磊 , 夏鹏飞 , 等 . 基于铁死亡理论的中医药防治肿瘤研究进展 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 22 ): 222 - 231 .
TARANGELO A , MAGTANONG L , BIEGING-ROLETT K T , et al . p53 Suppresses metabolic stress-induced ferroptosis in cancer cells [J]. Cell Rep , 2018 , 22 ( 3 ): 569 - 575 .
JIANG L , KON N , LI T , et al . Ferroptosis as a p53-mediated activity during tumour suppression [J]. Nature , 2015 , 520 ( 7545 ): 57 - 62 .
OU Y , WANG S J , LI D , et al . Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses [J]. Proc Natl Acad Sci USA , 2016 , 113 ( 44 ): E6806 - E6812 .
XIE Y , ZHU S , SONG X , et al . The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity [J]. Cell Rep , 2017 , 20 ( 7 ): 1692 - 1704 .
GONG D , CHEN M , WANG Y , et al . Role of ferroptosis on tumor progression and immunotherapy [J]. Cell Death Discov , 2022 , 8 ( 1 ): 427 .
WANG X , CHEN X , ZHOU W , et al . Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/Nrf2 pathways [J]. Acta Pharm Sin B , 2022 , 12 ( 2 ): 708 - 722 .
付佳琪 , 于栋华 , 陈平平 , 等 . 铁死亡在心血管疾病中的作用及中药干预研究进展 [J]. 中药药理与临床 , 2023 , 39 ( 2 ): 93 - 101 .
DOLL S , FREITAS F P , SHAH R , et al . FSP1 is a glutathione-independent ferroptosis suppressor [J]. Nature , 2019 , 575 ( 7784 ): 693 - 698 .
LENZEN S . Oxidative stress: The vulnerable beta-cell [J]. Biochem Soc Trans , 2008 , 36 ( Pt 3 ): 343 - 347 .
STANCIC A , SAKSIDA T , MARKELIC M , et al . Ferroptosis as a novel determinant of β -cell death in diabetic conditions [J]. Oxid Med Cell Longev , 2022 , 2022 : 3873420 .
DENG Q , ZHU Y , ZHANG M , et al . Ferroptosis as a potential new therapeutic target for diabetes and its complications [J]. Endocr Connect , 2023 , 12 ( 3 )
BRUNI A , PEPPER A R , PAWLICK R L , et al . Ferroptosis-inducing agents compromise in vitro human islet viability and function [J]. Cell Death Dis , 2018 , 9 ( 6 ): 595 .
ZHOU Y . The protective effects of cryptochlorogenic acid on β -cells function in diabetes in vivo and vitro via inhibition of ferroptosis [J]. Diabetes Metab Syndr Obes , 2020 , 13 : 1921 - 1931 .
连李斌 , 陈蓓 , 段蓓 . 芍药苷调节Akt/Nrf2/GPX4通路对妊娠糖尿病大鼠铁死亡的影响 [J]. 中国优生与遗传杂志 , 2023 , 31 ( 1 ): 22 - 26 .
JIA G , HILL M A , SOWERS J R . Diabetic cardiomyopathy:An update of mechanisms contributing to this clinical entity [J]. Circ Res , 2018 , 122 ( 4 ): 624 - 638 .
PAOLILLO S , MARSICO F , PRASTARO M , et al . Diabetic cardiomyopathy:Definition, diagnosis, and therapeutic implications [J]. Heart Fail Clin , 2019 , 15 ( 3 ): 341 - 347 .
武攸 , 吴仪伟 , 张珂承 , 等 . 铁死亡与糖尿病及其并发症的研究进展 [J]. 医学综述 , 2022 , 28 ( 12 ): 2448 - 2452 .
HU X , RAJESH M , ZHANG J , et al . Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2 [J]. Toxicol Lett , 2018 , 287 : 131 - 141 .
WANG G , SONG X , ZHAO L , et al . Resveratrol prevents diabetic cardiomyopathy by increasing Nrf2 expression and transcriptional activity [J]. Biomed Res Int , 2018 , 2018 : 2150218 .
彭可欣 . 青蒿素通过激活Nrf2抑制铁死亡减少ApoE -/- 糖尿病小鼠动脉粥样硬化 [D]. 衡阳 : 南华大学 , 2021 .
马振旺 , 姜德友 , 胡丙成 , 等 . 白藜芦醇通过HSF1介导的铁死亡改善糖尿病心肌细胞损伤的机制研究 [J]. 海南医学院学报 , 2022 , 28 ( 6 ): 406 - 411,419 .
BRENNER B M , COOPER M E , DE ZEEUW D , et al . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [J]. N Engl J Med , 2001 , 345 ( 12 ): 861 - 869 .
REMUZZI G , BERTANI T . Pathophysiology of progressive nephropathies [J]. N Engl J Med , 1998 , 339 ( 20 ): 1448 - 1456 .
WANG Y , BI R , QUAN F , et al . Ferroptosis involves in renal tubular cell death in diabetic nephropathy [J]. Eur J Pharmacol , 2020 , 888 : 173574 .
LI S , ZHENG L , ZHANG J , et al . Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy [J]. Free Radic Biol Med , 2021 , 162 : 435 - 449 .
KIM S , KANG S W , JOO J , et al . Correction:Characterization of ferroptosis in kidney tubular cell death under diabetic conditions [J]. Cell Death Dis , 2021 , 12 ( 4 ): 382 .
中华医学会内分泌学分会 . 非酒精性脂肪性肝病与相关代谢紊乱诊疗共识(第二版) [J]. 临床肝胆病杂志 , 2018 , 34 ( 10 ): 2103 - 2108 .
ZHU Z , ZHANG Y , HUANG X , et al . Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4 [J]. Eur J Pharmacol , 2021 , 908 : 174351 .
LI X , WANG T X , HUANG X , et al . Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity [J]. Liver Int , 2020 , 40 ( 6 ): 1378 - 1394 .
QI J , KIM J W , ZHOU Z , et al . Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice [J]. Am J Pathol , 2020 , 190 ( 1 ): 68 - 81 .
AI X , YU P , HOU Y , et al . A review of traditional Chinese medicine on treatment of diabetic retinopathy and involved mechanisms [J]. Biomed Pharmacother , 2020 , 132 : 110852 .
MOOS W H , FALLER D V , GLAVAS I P , et al . Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury [J]. Biochem Pharmacol , 2022 , 203 : 115168 .
TANG X , LI X , ZHANG D , et al . Astragaloside-Ⅳ alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2 [J]. Bioengineered , 2022 , 13 ( 4 ): 8240 - 8254 .
胡熳 . 和厚朴酚对糖尿病周围神经病变的保护作用及机制研究 [D]. 武汉 : 湖北大学 , 2023 .
张丽媛 . Nrf2在高糖高脂致胰岛 β 细胞损伤的作用机制研究及葡萄籽原花青素的干预作用 [D]. 石河子 : 石河子大学 , 2022 .
王同玲 . 葡萄籽原花青素通过Xc - /GPX4通路拮抗高糖高脂诱导的MIN6细胞铁死亡 [D]. 石河子 : 石河子大学 , 2022 .
ZHANG X , JIANG L , CHEN H , et al . Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress- related PERK pathway in MIN6 cells [J]. Toxicology , 2022 , 465 : 153048 .
杨素清 , 何天乐 , 苏军华 , 等 . 五味子乙素调控Nrf2/HO-1/GPX4铁死亡途径减轻糖尿病小鼠心肌损伤的机制研究 [J]. 中药材 , 2022 , 45 ( 7 ): 1705 - 1713 .
WU S , ZHU J , WU G , et al . 6-Gingerol alleviates ferroptosis and inflammation of diabetic cardiomyopathy via the Nrf2/HO-1 pathway [J]. Oxid Med Cell Longev , 2022 , 2022 : 3027514 .
WEI Z , SHAOHUAN Q , PINFANG K , et al . Curcumin attenuates ferroptosis-induced myocardial injury in diabetic cardiomyopathy through the Nrf2 pathway [J]. Cardiovasc Ther , 2022 , 2022 : 3159717 .
TAN H , CHEN J , LI Y , et al . Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways [J]. Mol Med , 2022 , 28 ( 1 ): 58 .
王玉军 , 王珍 , 赵天琪 , 等 . 甘草酸对高糖诱导小鼠足细胞损伤的影响 [J]. 宁夏医科大学学报 , 2022 , 44 ( 3 ): 267 - 271 .
CHEN J , OU Z , GAO T , et al . Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy [J]. Biomed Pharmacother , 2022 , 156 : 113953 .
WANG X , LI Q , SUI B , et al . Schisandrin A from schisandra chinensis attenuates ferroptosis and NLRP3 inflammasome-mediated pyroptosis in diabetic nephropathy through mitochondrial damage by AdipoR1 ubiquitination [J]. Oxid Med Cell Longev , 2022 , 2022 : 5411462 .
HUANG D , SHEN P , WANG C , et al . Calycosin plays a protective role in diabetic kidney disease through the regulation of ferroptosis [J]. Pharm Biol , 2022 , 60 ( 1 ): 990 - 996 .
张新 , 陈文娜 , 宋囡 , 等 . 黄芪甲苷对棕榈酸诱导的小鼠RAW264.7细胞铁死亡的调控作用 [J]. 中国病理生理杂志 , 2022 , 38 ( 6 ): 1105 - 1112 .
孙玉婷 . 芍药苷通过调控铁死亡减轻糖尿病肝损伤 [D]. 合肥 : 安徽医科大学 , 2022 .
JIANG J J , ZHANG G F , ZHENG J Y , et al . Targeting mitochondrial ROS-mediated ferroptosis by quercetin alleviates high-fat diet-induced hepatic lipotoxicity [J]. Front Pharmacol , 2022 , 13 : 876550 .
GAO G , XIE Z , LI E W , et al . Dehydroabietic acid improves nonalcoholic fatty liver disease through activating the Keap1/Nrf2-ARE signaling pathway to reduce ferroptosis [J]. J Nat Med , 2021 , 75 ( 3 ): 540 - 552 .
JIANG Z , SUN H , MIAO J , et al . The natural flavone acacetin protects against high-fat diet-induced lipid accumulation in the liver via the endoplasmic reticulum stress/ferroptosis pathway [J]. Biochem Biophys Res Commun , 2023 , 640 : 183 - 191 .
余洁英 , 林育浩 , 周凤华 , 等 . 葛根芩连汤对糖尿病湿热型小鼠心脏舒张功能的影响 [J]. 中国中药杂志 , 2022 , 47 ( 10 ): 2705 - 2711 .
李艳春 . 中药复方益糖康调控SLC7A11/GPX4介导的铁死亡防治糖尿病肾脏损伤的机制研究 [D]. 沈阳 : 辽宁中医药大学 , 2022 .
李二稳 , 高改 , 王梦瑶 , 等 . 泽泻汤抑制肝细胞铁死亡改善非酒精性脂肪性肝病的作用机制 [J]. 中医学报 , 2022 , 37 ( 6 ): 1243 - 1253 .
张新 , 陈文娜 , 宋囡 , 等 . 丹蒌片通过铁死亡途径减轻非酒精性脂肪性肝病模型小鼠肝脏氧化损伤 [J]. 中国病理生理杂志 , 2021 , 37 ( 12 ): 2180 - 2188 .
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