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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (6): 19-26.doi: 10.6040/j.issn.1671-7554.0.2024.1088

• 临床医学 • 上一篇    

银杏叶片联合曲美他嗪治疗老年慢性心力衰竭的效果及机制

贾魁,李治国,程翠婷,李志娟,刘瑞卿   

  1. 河南科技大学临床医学院 河南科技大学第一附属医院心血管内科, 河南 洛阳 471003
  • 发布日期:2025-07-08
  • 通讯作者: 李志娟. E-mail:3838836086@126.com
  • 基金资助:
    河南省医学科技攻关计划联合共建项目(LHGJ20190556)

Efficacy and mechanism of ginkgo leaf tablets combined with trimetazidine in the treatment of elderly patients with chronic heart failure

JIA Kui, LI Zhiguo, CHENG Cuiting, LI Zhijuan, LIU Ruiqing   

  1. Clinical Medicine School of Henan University of Science and Technology, Cardiovascular Department of the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, Henan, China
  • Published:2025-07-08

摘要: 目的 探讨银杏叶片联合曲美他嗪治疗老年慢性心力衰竭(chronic heart failure, CHF)的临床疗效及其对外周血单个核细胞(peripheral blood mononuclear cells, PBMCs)转化生长因子-β1(transforming growth factor-β1, TGF-β1)/Smad3信号通路分子mRNA表达的影响。 方法 选取2021年1月至2023年10月收治的96例老年CHF患者,随机分为联合组、曲美他嗪组和银杏叶片组,每组32例。比较3组患者的临床疗效、心功能指标(包括心脏指数、左室射血分数、左室收缩末期内径和左室舒张末期内径)、心力衰竭相关生物生物标志物(氨基末端B型利钠肽前体、可溶性基质裂解素2、血管紧张素Ⅱ)水平以及PBMCs中TGF-β1/Smad3通路关键分子(TGF-β1、Smad2、Smad3、Smad7)的mRNA相对表达量,并记录不良反应发生情况。 结果 联合组患者的心脏指数和左室射血分数高于曲美他嗪组和银杏叶片组,且曲美他嗪组高于银杏叶片组,差异有统计学意义(P<0.05);联合组患者的左室收缩末期内径和左室舒张末期内径低于曲美他嗪组和银杏叶片组,且曲美他嗪组低于银杏叶片组,差异有统计学意义(P<0.05)。联合组患者的氨基末端B型利钠肽前体、可溶性基质裂解素2、血管紧张素Ⅱ水平低于曲美他嗪组和银杏叶片组,且曲美他嗪组低于银杏叶片组,差异有统计学意义(P<0.05)。 联合组患者的PBMCs中TGF-β1、Smad2、Smad3的mRNA相对表达量低于曲美他嗪组和银杏叶片组;Smad7 mRNA的相对表达量高于曲美他嗪组和银杏叶片组,差异均有统计学意义(P<0.05)。3组患者的不良反应发生率差异无统计学意义(P>0.05)。 结论 银杏叶片联合曲美他嗪可显著改善老年CHF患者的心功能并减轻心肌损伤,其机制与抑制TGF-β1/Smad3信号通路有关,为中西医联合治疗CHF提供了新策略。

关键词: 老年慢性心力衰竭, 银杏叶片, 曲美他嗪, 转化生长因子-β1, 左室射血分数, 氨基末端B型利钠肽前体

Abstract: Objective To investigate the clinical efficacy of ginkgo leaf tablets combined with trimetazidine in the treatment of elderly patients with chronic heart failure(CHF)and its impact on the mRNA expression of transforming growth factor-β1(TGF-β1)/Smad3 signaling pathway molecules in peripheral blood mononuclear cells(PBMCs). Methods Ninety-six elderly patients with CHF were selected from January 2021 to October 2023 and randomly assigned to a combination group, a trimetazidine group, and a ginkgo leaf tablet group, with 32 patients in each group. The clinical efficacy, cardiac function indicators(including cardiac index, left ventricular ejection fraction, left ventri-cular end-systolic diameter, and left ventricular end-diastolic diameter), levels of heart failure-related biomarkers(amino-terminal pro-B-type natriuretic peptide, soluble stromal derived factor 2, angiotensin II), and mRNA relative expression levels of key molecules in the TGF-β1/Smad3 pathway(TGF-β1, Smad2, Smad3, Smad7)in PBMCs were compared among the three groups, and the occurrence of adverse reactions was recorded. Results The cardiac index and left ventricular ejection fraction in the combination group were higher than those in the trimetazidine group and ginkgo leaf tablet group, and the trimetazidine group had higher values than the ginkgo leaf tablet group, with statistically significant differences(P<0.05). The left ventricular end-systolic diameter and left ventricular end-diastolic diameter in the combination group were lower than those in the trimetazidine group and ginkgo leaf tablet group, and the trimetazidine group had lower values than the ginkgo leaf tablet group, with statistically significant differences(P<0.05). The levels of amino-terminal pro-brain natriuretic peptide, soluble stromal derived factor 2, and angiotensin II in the combination group were lower than those in the trimetazidine group and ginkgo leaf tablet group, and the trimetazidine group had lower values than the ginkgo leaf tablet group, with statistically significant differences(P<0.05). The relative mRNA expression levels of TGF-β1, Smad2, and Smad3 in PBMCs from the combination group were lower than those in the trimetazidine group and ginkgo leaf tablet group; the relative mRNA expression level of Smad7 was higher than that in the trimetazidine group and ginkgo leaf tablet group, with statistically significant differences(P<0.05). There was no statistically significant difference in the incidence of adverse reactions among the three groups(P>0.05). Conclusions The combination of Ginkgo leaf tablets and trimetazidine can significantly improve cardiac function and alleviate myocardial damage in elderly patients with CHF. The mechanism is related to the inhibition of the TGF-β1/Smad3 signaling pathway, providing a new strategy for the integrated traditional Chinese and Western medicine treatment of CHF.

Key words: Elderly chronic heart failure, Ginkgo leaf tablets, Trimetazidine, Transforming growth factor-β1, Left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide

中图分类号: 

  • R543
[1] 徐佳慧, 胡世莲. 慢性心力衰竭的流行病学与预防措施[J].中国临床保健杂志, 2021, 24(6): 721-725. XU Jiahui, HU Shilian. The epidemiology and prevention of chronic heart failure [J]. Chinese Journal of Clinical Healthcare, 2021, 24(6): 721-725.
[2] He Y, Dai MS, Tao LY, et al. Pericarpium trichosanthis inhibits TGF-β1-Smad3 pathway-induced cardiac fibrosis in heart failure rats via upregulation of microRNA-29b[J]. J Gene Med, 2025, 27(1): e70003-e70013.
[3] 曾宪育. 曲美他嗪联合美托洛尔治疗冠心病合并心力衰竭患者的效果[J]. 中国民康医学, 2024, 36(10): 22-25. ZENG Xianyu. Effects of Trimetazidine combined with Metoprolol in treatment of patients with coronary heart disease complicated with heart failure[J]. Medical Journal of Chinese Peoples Health, 2024, 36(10): 22-25.
[4] Zhang JM, He XJ, Bai XY, et al. Protective effect of trimetazidine in radiation-induced cardiac fibrosis in mice[J]. J Radiat Res, 2020, 61(5): 657-665.
[5] Li XX, Lu LY, Chen J, et al. New insight into the mechanisms of Ginkgo biloba extract in vascular aging prevention[J]. Curr Vasc Pharmacol, 2020, 18(4): 334-345.
[6] Tian JF, Liu Y, Chen KJ. Ginkgo biloba extract in vascular protection: molecular mechanisms and clinical applications[J]. Curr Vasc Pharmacol, 2017, 15(6): 532-548.
[7] 中华医学会, 中华医学会杂志社, 中华医学会全科医学分会, 等. 慢性心力衰竭基层诊疗指南(2019年)[J]. 中华全科医师杂志, 2019, 18(10): 936-947. Chinese Medical Association, Chinese Medical Journals Publishing House, Chinese Society of General Practice, et al. Guideline for primary care of chronic heart failure(2019)[J]. Chinese Journal of General Practitioners, 2019, 18(10): 936-947.
[8] 陈可冀, 吴宗贵, 朱明军, 等. 慢性心力衰竭中西医结合诊疗专家共识[J]. 心脑血管病防治, 2016, 16(5): 340-347.
[9] Xu WP, Wang WZ, Xiao QM, et al. Effect of recombinant human brain natriuretic peptide on acute carbon monoxide poisoning complicated with heart failure with reduced ejection fraction[J]. Int Heart J, 2022, 63(2): 312-318.
[10] 李瑾, 刘江峰, 符赵鑫. 不同剂量曲美他嗪辅助治疗扩张型心肌病心力衰竭患者的疗效比较及血清相关细胞因子水平分析[J]. 岭南心血管病杂志, 2023, 29(2): 180-183, 189. LI Jin, LIU Jiangfeng, FU Zhaoxin. Comparison of efficacy of different doses of trimetazidine in adjuvant treatment of heart failure patients with dilated cardiomyopathy and analysis of serum related cytoki[J]. South China Journal of Cardiovascular Diseases, 2023, 29(2): 180-183, 189.
[11] 韩树, 钟利群. 银杏叶片对脑梗死合并高血压患者凝血功能及血清MCP-1、MCPIP1的影响[J]. 中国循证心血管医学杂志, 2023, 15(3): 345-347. HAN Shu, ZHONG Liqun. Influence of Ginkgo Leaf Tablets on coagulation function and levels of serum MCP-1 and MCPIP1 inpatients with cerebral infarction complicated by hypertension[J]. Chinese Journal of Evidence-Based Cardiovascular Medicine, 2023, 15(3): 345-347.
[12] 尹晓东, 张刚, 刘日辉, 等. 氯吡格雷联合曲美他嗪对冠心病合并心力衰竭患者的疗效[J]. 西北药学杂志, 2021, 36(3): 463-466. YIN Xiaodong, ZHANG Gang, LIU Rihui, et al. Effect of clopidogrel combined with trimetazidine in patients with coronary heart disease and heart failure[J]. Northwest Pharmaceutical Journal, 2021, 36(3): 463-466.
[13] 普顺华, 蒋兴玲, 郑甲林, 等. 沙库巴曲缬沙坦联合曲美他嗪治疗慢性充血性心力衰竭临床疗效观察[J]. 重庆医学, 2020, 49(4): 539-543. PU Shunhua, JIANG Xingling, ZHENG Jialin, et al. Therapeatic effect of Sacubitril Valsartan combined with Trimetazidine on chronic congestive heart failure[J]. Chongqing Medicine, 2020, 49(4): 539-543.
[14] 董媛, 原巧宁, 杨永辉. 银杏叶片联合沙库巴曲缬沙坦治疗老年慢性心力衰竭的疗效及对血清NT-proBNP、MMP-9、IL-6和RBP4水平的影响[J]. 中国医师杂志, 2023, 25(9): 1373-1376.
[15] 张婷婷, 郭佳. 基于心脏彩超评价银杏叶提取物联合奥美沙坦酯治疗慢性充血性心力衰竭的临床疗效[J]. 中西医结合心脑血管病杂志, 2020, 18(1): 111-113. ZHANG Tingting, GUO Jia. Evaluation of clinical efficacy of Ginkgo biloba extract combined with olmesartan medoxomil in the treatment of chronic congestive heart failure based on cardiac color Doppler ultrasound[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2020, 18(1): 111-113.
[16] Li X, Guo DX, Zhou HL, et al. Pro-inflammatory cytokines, oxidative stress and diffuse coronary reocclusions in elderly patients after coronary stenting[J]. Cytokine, 2020, 129(1): 155028-155038.
[17] Shu HY, Hang WJ, Peng YZ, et al. Trimetazidine attenuates heart failure by improving myocardial metabolism via AMPK[J]. Front Pharmacol, 2021, 12(15): 707399-707409.
[18] Xing XT, Kong MZ, Hou QY, et al. Effects of Ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism[J]. Pharm Biol, 2022, 60(1): 1190-1197.
[19] Liu M, Ai J, Feng J, et al. Effect of paeoniflorin on cardiac remodeling in chronic heart failure rats through the transforming growth factor β1/Smad signaling pathway[J]. Cardiovasc Diagn Ther, 2019, 9(3): 272-280.
[20] Vivar R, Humeres C, Anfossi R, et al. Role of FoxO3a as a negative regulator of the cardiac myofibroblast conversion induced by TGF-β1[J]. Biochim Biophys Acta Mol Cell Res, 2020, 1867(7): 118695-118705.
[21] Hu SY, Zhou Y, Zhong SJ, et al. Shenmai injection improves hypertensive heart failure by inhibiting myocardial fibrosis via TGF-β 1/smad pathway regulation[J]. Chin J Integr Med, 2023, 29(2): 119-126.
[22] Wei CY, Zhang YS, Zhong XB, et al. Ginkgo Biloba leaf extract mitigates cisplatin-induced chronic renal interstitial fibrosis by inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells mediated by the Smad3/TGF-β1 and Smad3/p38 MAPK pathways[J]. Chin Med, 2022, 17(1): 25-35.
[23] 姜华, 赵薇, 刘丹, 等. 单硝酸异山梨酯注射液联合曲美他嗪对慢性收缩性心力衰竭患者血清相关因子及心功能的影响[J]. 西部医学, 2018, 30(8): 1166-1170. JIANG Hua, ZHAO Wei, LIU Dan, et al. Effects of isosorbide mononitrate injection and trimetazidine on serum levels of sICAM-1, ICAM-1, TGF-beta 1 and cardiac function in patients with chronic systolic heart failure[J]. Medical Journal of West China, 2018, 30(8): 1166-1170.
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