张梦鸽,崔璐,林立志,申程,曹勇

• 1:济宁医学院临床医学院
• 2:济宁市冠脉介入精准治疗研究重点实验室
• 3:济宁医学院附属医院心内科冠心病二病区

摘要(Abstract)：

冠心病（CHD）是一种严重威胁人类健康的心血管病。其核心发病机制为冠状动脉粥样硬化导致血管壁增厚、硬化，管腔逐渐狭窄甚至闭塞。CHD在心血管病中占比较高，显著降低患者的生活质量并缩短其预期寿命。达格列净是一种新型的降糖药物，属于钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i），通过减少肾小管对葡萄糖的重吸收、增加葡萄糖在尿液中的排出实现降低血糖。除降血糖外，达格列净还可以通过调节血脂、抗炎、调节氧化应激、抑制血小板活化、减少心肌细胞凋亡、抑制纤维化、促进血管生成等作用，对心脏发挥保护作用。目前达格列净在心力衰竭的治疗中已经得到广泛应用，随着对达格列净研究的深入，发现其也能使CHD患者获益，现对达格列净在CHD领域的应用进展作一综述。

关键词(KeyWords)： 冠心病;达格列净;机制

Abstract:

Keywords:

基金项目(Foundation): 济宁市重点研发计划项目（2024YXNS068）;; 济宁医学院附属医院主诊医师团队专项临床研究计划项目（ZZTD-2022-002）

作者(Author): 张梦鸽,崔璐,林立志,申程,曹勇

参考文献(References)：

• [1] Shaya GE,Leucker TM,Jones SR,et al.Coronary heart disease risk:low-density lipoprotein and beyond[J].Trends Cardiovasc Med,2022,32(4):181-194.DOI:10.1016/j.tcm.2021.04.002.
• [2]张茜,叶豪奕,崔思美,等.动脉粥样硬化易损斑块分子影像探针研究:进展、挑战与展望[J].中国介入心脏病学杂志,2025,33(4):215-221.DOI:10.3969/j.issn.1004-8812.2025.04.005.
• [3]Petrie MC,Verma S,Docherty KF,et al.Effect of Dapagliflozinon worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes[J].JAMA,2020,323(14):1353-1368.DOI:10.1001/jama.2020.1906.
• [4] Tanday N,Irwin N,Flatt PR,et al.Dapagliflozin exerts positive effects on beta cells,decreases glucagon and does not alter beta-to alpha-cell transdifferentiation in mouse models of diabetes and insulin resistance[J].Biochem Pharmacol,2020,177:114009.DOI:10.1016/j.bcp.2020.114009.
• [5]Wei R,Cui X,Feng J,et al.Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice[J].Metabolism,2020,111:154324.DOI:10.1016/j.metabol.2020.154324.
• [6]Meier JJ.GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus[J].Nat Rev Endocrinol,2012,8(12):728-742.DOI:10.1038/nrendo.2012.140.
• [7] PodestàMA,Sabiu G,Galassi A,et al.SGLT2 inhibitors in diabetic and non-diabetic chronic kidney disease[J].Biomedicines,2023,11(2):279.DOI:10.3390/biomedicines11020279.
• [8]Kohlmorgen C,Gerfer S,Feldmann K,et al.Dapagliflozin reduces thrombin generation and platelet activation:implications for cardiovascular risk reduction in type 2 diabetes mellitus[J].Diabetologia,2021,64(8):1834-1849.DOI:10.1007/s00125-021-05498-0.
• [9]Li J,Li C,Feng X,et al.SGLT2 inhibition,blood lipids,and cardiovascular disease:a Mendelian randomization study[J].ESC Heart Fail,2024,11(6):3960-3971.DOI:10.1002/ehf2.14987.
• [10]Huang X,Wang Y,Wan R,et al.Identification of lipid metabolismrelated genes in Dapagliflozin treated rats with diabetic cardiomyopathy by bioinformatics[J].Front Endocrinol(Lausanne),2025,16:1525831.DOI:10.3389/fendo.2025.1525831.
• [11]Le Jemtel TH,Samson R,Ayinapudi K,et al.Epicardial adipose tissue and cardiovascular disease[J].Curr Hypertens Rep,2019,21(5):36.DOI:10.1007/s11906-019-0939-6.
• [12]Cinti F,Leccisotti L,Sorice GP,et al.Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes[J].Cardiovasc Diabetol,2023,22(1):349.DOI:10.1186/s12933-023-02091-0.
• [13]Sato T,Aizawa Y,Yuasa S,et al.The effect of Dapagliflozin treatment on epicardial adipose tissue volume[J].Cardiovasc Diabetol,2018,17(1):6.DOI:10.1186/s12933-017-0658-8.
• [14]Sato T,Aizawa Y,Yuasa S,et al.The effect of Dapagliflozin treatment on epicardial adipose tissue volume and P-wave indices:an ad-hoc analysis of the previous randomized clinical trial[J].J Atheroscler Thromb,2020,27(12):1348-1358.DOI:10.5551/jat.48009.
• [15]Díaz-Rodríguez E,Agra RM,Fernández??L,et al.Effects of Dapagliflozin on human epicardial adipose tissue:modulation of insulin resistance,inflammatory chemokine production,and differentiation ability[J].Cardiovasc Res,2018,114(2):336-346.DOI:10.10 9 3/cvr/cvx186.
• [16]Lee TM,Chang NC,Lin SZ.Dapagliflozin,a selective SGLT2 inhibitor,attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts[J].Free Radic Biol Med,2017,104:298-310.DOI:10.1016/j.freeradbiomed.2017.01.035.
• [17]Tepebasi MY,Selcuk E,Taner R,et al.Potential ameliorative effect of Dapagliflozin on systemic inflammation-induced cardiovascular injury via endoplasmic reticulum stress and autophagy pathway[J].Mol Biol Rep,2024,51(1):1080.DOI:10.1007/s11033-024-09990-9.
• [18]Han X,Liu X,Zhao X,et al.Dapagliflozin amelioratessepsis-induced heart injury by inhibiting cardiomyocyte apoptosis and electrical remodeling through the PI3K/AKT pathway[J].Eur J Pharmacol,2023,955:175930.DOI:10.1016/j.ejphar.2023.175 930.
• [19]IonicǎLN,Buriman DG,Linta AV,et al.Empagliflozin and Dapagliflozin decreased atrial monoamine oxidase expression and alleviated oxidative stress in overweight non-diabetic cardiac patients[J].Mol Cell Biochem,2025,480(3):1645-1655.DOI:10.1007/s 11010-024-05076-z.
• [20] Alsereidi FR,Khashim Z,Marzook H,et al.Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes,aortic endothelial cells,and stem cell-derived β cells[J].Cardiovasc Diabetol,2024,23(1):388.DOI:10.1186/s12933-024-02481-y.
• [21]Zhou Y,Tai S,Zhang N,et al.Dapagliflozin prevents oxidative stress-induced endothelial dysfunction via sirtuin 1activation[J].Biomed Pharmacother,2023,165:115213.DOI:10.1016/j.biopha.2023.115213.
• [22]Ma HX,Wu K,Dong FH,et al.Effects of Empagliflozin and Dapagliflozin in alleviating cardiac fibrosis through SIRT6-mediated oxidative stress reduction[J].Sci Rep,2024,14(1):30764.DOI:10.1038/s41598-024-80829-w.
• [23] Lin YH,Tsai WC,Chiu CC,et al.The beneficial effect of the SGLT2 inhibitor Dapagliflozin in alleviating acute myocardial infarction-induced cardiomyocyte injury by increasing the Sirtuin family SIRT1/SIRT3 and cascade signaling[J].Int J Mol Sci,2024,25(15):8541.DOI:10.3390/ijms25158541.
• [24]Finley LW,Carracedo A,Lee J,et al.SIRT3 opposes reprogramming of cancer cell metabolism through HIF1 αdestabilization[J].Cancer Cell,2011,19(3):416-428.DOI:10.1016/j.ccr.2011.02.014.
• [25]Cheng Y,Ren X,Gowda AS,et al.Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress[J].Cell Death Dis,2013,4(7):e731.DOI:10.1038/cddis.2013.254.
• [26] Zhao X,Liu Y,Han X,et al.Dapagliflozin attenuates the vulnerability to atrial fibrillation in rats with lipopolysaccharide-induced myocardial injury[J].Int Immunopharmacol,2023,125(Pt A):111038.DOI:10.1016/j.intimp.2023.111038.
• [27]Pan H,Guan D,Liu X,et al.SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2[J].Cell Res,2016,26(2):190-205.DOI:10.103 8/cr.2016.4.
• [28]Ye Y,Jia X,Bajaj M,et al.Dapagliflozin attenuates Na~+/H+exchanger-1 in cardiofibroblasts via AMPK activation[J].Cardiovasc Drugs Ther,2018,32(6):553-558.DOI:10.1007/s10557-018-6837-3.
• [29]Luo J,Li L,Zeng Q.Effects of Dapagliflozin in combination with Hydrochlorothiazide on cardiac remodeling in rats with heart failure after myocardial infarction[J].Int Heart J,2024,65(5):913-928.DOI:10.1536/ihj.24-069.
• [30] Eldesoqui M,Eldken ZH,Mostafa SA,et al.Exercise augments the effect of SGLT2 inhibitor Dapagliflozin on experimentally induced diabetic cardiomyopathy,possible underlying mechanisms[J].Metabolites,2022,12(7):635.DOI:10.3390/metabo12070635.
• [31]Kraakman MJ,Lee MK,Al-Sharea A,et al.Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes[J].J Clin Invest,2017,127(6):2133-2147.DOI:10.1172/JCI92450.
• [32]Spigoni V,Fantuzzi F,Carubbi C,et al.Sodium-glucosecotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets:potential relevance to prevention of cardiovascular events[J].Cardiovasc Diabetol,2020,19(1):46.DOI:10.1186/s12933-020-01016-5.
• [33]Lescano CH,Leonardi G,Torres PHP,et al.The sodium-glucose cotransporter-2(SGLT2)inhibitors synergize with nitric oxide and prostacyclin to reduce human platelet activation[J].Biochem Pharmacol,2020,182:114276.DOI:10.1016/j.bcp.2020.114276.
• [34]Fan ZG,Xu Y,Chen X,et al.Appropriate dose of Dapagliflozin improves cardiac outcomes by normalizing mitochondrial fission and reducing cardiomyocyte apoptosis after acute myocardial infarction[J].Drug Design,Development and Therapy,2022,16:2017-2030.DOI:10.2147/DDDT.S371506.
• [35]Peng Y,Guo M,Luo M,et al.Dapagliflozin ameliorates myocardial infarction injury through AMPK α-dependent regulation of oxidative stress and apoptosis[J].Heliyon,2024,10(7):e29160.DOI:10.1016/j.heliyon.2024.e29160.
• [36]Zhang X,Wang N,Fu P,et al.Dapagliflozin attenuates heart failure with preserv ed ejection fraction remodeling and dysfunction by elevating β-hydroxybutyrate-activated citrate synthase[J].J Cardiovasc Pharmacol,2023,82(5):375-388.DOI:10.1097/FJC.0000000000001474.
• [37]Wang K,Li Z,Sun Y,et al.Dapagliflozin improves cardiac function,remodeling,myocardial apoptosis,and inflammatory cytokines in mice with myocardial infarction[J].J Cardiovasc Transl Res,2022,15(4):786-796.DOI:10.1007/s12265-021-10192-y.
• [38]Nikolaou PE,Mylonas N,Makridakis M,et al.Cardioprotection by selective SGLT2 inhibitors in a non-diabetic mouse model of myocardial ischemia/reperfusion injury:a class or a drug effect?[J].Basic Res Cardiol,2022,117(1):27.DOI:10.1007/s00395-022-00934-7.
• [39]Zhou Y,Zhu X,Cui H,et al.The role of the VEGF family in coronary heart disease[J].Front Cardiovasc Med,2021,8:738325.DOI:10.3389/fcvm.2021.738325.
• [40]Wu X,Reboll MR,Korf-Klingebiel M,et al.Angiogenesis after acute myocardial infarction[J].Cardiovasc Res,2021,117(5):1257-1273.DOI:10.1093/cvr/cvaa287.
• [41]Wang M,Liu X,Ding B,et al.SGLT2 inhibitor Dapagliflozin alleviates cardiac dysfunction and fibrosis after myocardial infarction by activating PXR and promoting angiogenesis[J].Biomed Pharmacother,2024,177:116994.DOI:10.1016/j.biopha.2024.116994.
• [42]Yang H,Lan W,Liu W,et al.Dapagliflozin promotes angiogenesis in hindlimb ischemia mice by inducing M2macrophage polarization[J].Front Pharmacol,2023,14:1255904.DOI:10.3389/fphar.2023.1255904.
• [43] Han L,Ye G,Su W,et al.Dapagliflozin improves angiogenesis after hindlimb ischemia through the PI3K-AKT-eNOS pathway[J].Biomolecules,2024,14(5):592.DOI:10.3390/biom14050592.
• [44] Chen B,Guo J,Ye H,et al.Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling(Review)[J].Mol Med Rep,2024,29(5):73.DOI:10.3 892/mmr.2024.13197.
• [45]Maulik SK,Mishra S.Hypertrophy to failure:what goes wrong with the fibers of the heart?[J].Indian Heart J,2015,67(1):66-69.DOI:10.1016/j.ihj.2015.02.012.
• [46]Packer M.Mutual antagonism of hypoxia-inducible factor isoforms in cardiac,vascular,and renal disorders[J].JACCBasic Transl Sci,2020,5(9):961-968.DOI:10.1016/j.jacbts.2020.05.006.
• [47]Yang Z,Li T,Xian J,et al.SGLT2 inhibitor Dapagliflozin attenuates cardiac fibrosis and inflammation by reverting the HIF-2αsignaling pathway in arrhythmogenic cardiomyopathy[J].FASEB J,2022,36(7):e22410.DOI:10.1096/fj.202200243R.
• [48]Ma S,Chen L,Yan J,et al.Dapagliflozin attenuates residual cardiac remodeling after surgical ventricular reconstruction in mice with an enlarged heart after myocardial infarction[J].Biomed Pharmacother,2022,156:113765.DOI:10.1016/j.biopha.2022.113765.
• [49]Prattichizzo F,De Nigris V,Micheloni S,et al.Increases in circulating levels of ketone bodies and cardiovascular protection with SGLT2 inhibitors:is low-grade inflammation the neglected component?[J].Diabetes Obes Metab,2018,20(11):2515-2522.DOI:10.1111/dom.13488.
• [50] Zhao Y,Xu L,Tian D,et al.Effects of sodium-glucose co-transporter 2(SGLT2)inhibitors on serum uric acid level:a meta-analysis of randomized controlled trials[J].Diabetes Obes Metab,2018,20(2):458-462.DOI:10.1111/dom.13101.
• [51]Hao Z,Huang X,Shao H,et al.Effects of Dapagliflozin on serum uric acid levels in hospitalized type 2 diabetic patients with inadequate glycemic control:a randomized controlled trial[J].Ther Clin Risk Manag,2018,14:2407-2413.DOI:10.2147/TCRM.S186347.
• [52]Lin MJ,Zou SB,Zhu BX.Effect of Dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia[J].World J Clin Cases,2024,12(18):3468-3475.DOI:10.12998/wjcc.v12.i18.3468.
• [53] Pouralijan Amiri M,Khoshkam M,Salek RM,et al.Metabolomics in early detection and prognosis of acute coronary syndrome[J].Clin Chim Acta,2019,495:43-53.DOI:10.1016/j.cca.2019.03.1632.
• [54]James S,Erlinge D,Storey RF,et al.Rationale and design of the DAPA-MI trial:Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction[J].Am Heart J,2023,266:188-197.DOI:10.1016/j.ahj.2023.08.008.
• [55]Peikert A,Vaduganathan M.Sodium glucose co-transporter 2inhibition following acute myocardial infarction:the DAPA-MI and EMPACT-MI trials[J].JACC Heart Fail,2024,12(5):949-953.DOI:10.1016/j.jchf.2024.01.019.
• [56]Li S,Wang L,Wang P,et al.Dapagliflozin improves cardiac function and reduces adverse events in myocardial infarction:a meta-analysis in diabetic and non-diabetic populations[J].Front Endocrinol(Lausanne),2025,16:1594861.DOI:10.3389/fendo.2025.15 94861.
• [57] Dayem KA,Younis O,Zarif B,et al.Impact of Dapagliflozin on cardiac function following anterior myocardial infarction in non-diabetic patients-DACAMI(a randomized controlled clinical trial)[J].Int J Cardiol,2023,379:9-14.DOI:10.1016/j.ijcard.2023.03.002.
• [58]Zhou L,Geng X,Hu Q,et al.Effects of Dapagliflozin on cardiac function and short-term prognosis of patients with both acute myocardial infarction and type 2 diabetes mellitus[J].Minerva Cardiol Angiol,2024,72(3):292-298.DOI:10.23736/s2724-5683.23.06478-5.
• [59]Mao L,Cai D,Chi B,et al.Dapagliflozin reduces risk of heart failure rehospitalization in diabetic acute myocardial infarction patients:a propensity score-matched analysis[J].Eur J Clin Pharmacol,2023,79(7):915-926.DOI:10.1007/s00228-023-03495-3.
• [60]Deng L,Wang J,Deng Y,et al.Effect of Dapagliflozin on malignant ventricular arrhythmias in elderly after acute myocardial infarction:a propensity score-matched cohort study[J].Eur J Clin Pharmacol,2025,81(6):839-851.DOI:10.1007/s00228-025-03832-8.
• [61]郑瑜,李树仁,刘肖,等.ST段抬高型心肌梗死患者直接经皮冠状动脉介入治疗术后发生急性肾损伤的相关性分析[J].中国介入心脏病学杂志,2020,28(5):257-263.DOI:10.3969/j.issn.1004-8812.2020.05.004.
• [62] Cai D,Chen Q,Mao L,et al.Association of SGLT2 inhibitor Dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients[J].Eur J Clin Pharmacol,2024,80(4):613-620.DOI:10.1007/s00228-024-03623-7.
• [63]Karakasis P,Fragakis N,Kouskouras K,et al.Sodium-glucose cotransporter-2 inhibitors in patients with acute coronary syndrome:a modern Cinderella?[J].Clin Ther,2024,46(11):841-850.DOI:10.1016/j.clinthera.2024.06.010.
• [64]Wiviott SD,Raz I,Bonaca MP,et al.Dapagliflozin and cardiovascular outcomes in type 2 diabetes[J].N Engl J Med,2019,380(4):347-357.DOI:10.1056/NEJMoa1812389.
• [65]Zhu Y,Zhang JL,Yan XJ,et al.Effect of Dapagliflozin on the progno sis of patients with acute myocardial infarction undergoing percutaneous coronary intervention[J].Cardiovasc Diabetol,2022,21(1):186.DOI:10.1186/s12933-022-01627-0.
• [66]Curneen JM,Judge C,Traynor B,et al.Interhospital and interindividual variability in secondary prevention:a comparison of outpatients with a history of chronic coronary syndrome versus outpatients with a history of acute coronary syndrome(the iASPIRE Study)[J].Open Heart,2021,8(1):e001659.DOI:10.1136/openhrt-2021-001659.
• [67]谢昊泰,龚艳君.2024欧洲心脏病学会慢性冠状动脉综合征管理指南解读[J].中国介入心脏病学杂志,2024,32(12):661-669.DOI:10.3969/j.issn.1004-8812.2024.12.001.
• [68]刘先仕,李萍.2型糖尿病合并冠心病患者采用达格列净治疗的临床效果观察[J].中国实用医药,2024,19(12):102-106.DOI:10.14163/j.cnki.11-5547/r.2024.12.028.
• [69]Capece U,Pavanello C,Cinti F,et al.Dapagliflozin-induced myocardial flow reserve improvement is not associated with HDL ability to stimulate endothelial nitric oxide production[J].Diabetes Ther,2024,15(1):257-268.DOI:10.1007/s13300-023-01491-5.
• [70]Leccisotti L,Cinti F,Sorice GP,et al.Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes:the DAPAHEART trial:a preliminary report[J].Cardiovasc Diabetol,2022,21(1):173.DOI:10.1186/s12933-022-01607-4.
• [71]Alatawi AM.Metformin versus sodium glucose co-transporters inhibitors as first-line for atherosclerotic cardiovascular disease:a meta-analysis[J].Pak J Med Sci,2024,40(1Part-Ⅰ):209-213.DOI:10.12669/pjms.40.1.6982.
• [72] Akamine MAV,Ferreira Soares BMA,Telles JPM,et al.Role of Dapagliflozin in ischemic preconditioning in patients with symptomatic coronary artery Disease-DAPA-IP study protocol[J].Pharmaceuticals(Basel),2024,17(7):920.DOI:10.3390/ph17070920.
• [73]Cesaro A,Acerbo V,Vetrano E,et al.Sodium-glucose cotransporter 2 inhibitors in patients with diabetes and coronary artery disease:translating the benefits of the molecular mechanisms of gliflozins into clinical practice[J].Int J Mol Sci,2023,24(9):8099.DOI:10.3390/ijms24098099.