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姜黄素对心肌缺血/再灌注损伤的心脏保护作用:一项对临床前和临床研究的系统评价与荟萃分析

Cardioprotective effects of curcumin against myocardial I/R injury: A systematic review and meta-analysis of preclinical and clinical studies.

作者信息

Li Tianli, Jin Jialin, Pu Fenglan, Bai Ying, Chen Yajun, Li Yan, Wang Xian

机构信息

Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

National Integrated Traditional and Western Medicine Center for Cardiovascular Disease, China-Japan Friendship Hospital, Beijing, China.

出版信息

Front Pharmacol. 2023 Mar 9;14:1111459. doi: 10.3389/fphar.2023.1111459. eCollection 2023.

Abstract

Myocardial ischemia-reperfusion (I/R) injury is a complex clinical problem that often leads to further myocardial injury. Curcumin is the main component of turmeric, which has been proved to have many cardioprotective effects. However, the cardioprotective potential of curcumin remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of curcumin on myocardial I/R injury. Eight databases and three register systems were searched from inception to 1 November 2022. Data extraction, study quality assessment, data analyses were carried out strictly. Then a fixed or random-effects model was applied to analyze the outcomes. SYRCLE's-RoB tool and RoB-2 tool was used to assess the methodological quality of the included studies. RevMan 5.4 software and stata 15.1 software were used for statistical analysis. 24 animal studies, with a total of 503 animals, and four human studies, with a total of 435 patients, were included in this study. The meta-analysis of animal studies demonstrated that compared with the control group, curcumin significantly reduced myocardial infarction size ( < 0.00001), and improved the cardiac function indexes (LVEF, LVFS, LVEDd, and LVESd) ( < 0.01). In addition, the indexes of myocardial injury markers, myocardial oxidation, myocardial apoptosis, inflammation, and other mechanism indicators also showed the beneficial effect of curcumin ( < 0.05). In terms of clinical studies, curcumin reduced the incidence of cardiac dysfunction, myocardial infarction in the hospital and MACE in the short term, which might be related to its anti-inflammatory and anti-oxidative property. Dose-response meta-analysis predicted, 200 mg/kg/d bodyweight was the optimal dose of curcumin in the range of 10-200 mg/kg/d, which was safe and non-toxic according to the existing publications. Our study is the first meta-analysis that includes both preclinical and clinical researches. We suggested that curcumin might play a cardioprotective role in acute myocardial infarction in animal studies, mainly through anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis effects. In addition, from the clinical studies, we found that curcumin might need a longer course of treatment and a larger dose to protect the myocardium, and its efficacy is mainly reflected on reducing the incidence of myocardial infarction and MACE. Our finding provides some meaningful advice for the further research.

摘要

心肌缺血再灌注(I/R)损伤是一个复杂的临床问题,常常会导致进一步的心肌损伤。姜黄素是姜黄的主要成分,已被证明具有多种心脏保护作用。然而,姜黄素的心脏保护潜力仍不明确。本系统评价和荟萃分析旨在评估关于姜黄素对心肌I/R损伤影响的临床和临床前(动物模型)证据。检索了8个数据库和3个注册系统,检索时间从建库至2022年11月1日。严格进行数据提取、研究质量评估和数据分析。然后应用固定效应或随机效应模型分析结果。使用SYRCLE's-RoB工具和RoB-2工具评估纳入研究的方法学质量。使用RevMan 5.4软件和Stata 15.1软件进行统计分析。本研究纳入了24项动物研究,共503只动物,以及4项人体研究,共435例患者。动物研究的荟萃分析表明,与对照组相比,姜黄素显著减小了心肌梗死面积(<0.00001),并改善了心功能指标(左室射血分数、左室短轴缩短率、左室舒张末期内径和左室收缩末期内径)(<0.01)。此外,心肌损伤标志物、心肌氧化、心肌凋亡、炎症及其他机制指标也显示了姜黄素的有益作用(<0.05)。在临床研究方面,姜黄素降低了心脏功能障碍、院内心肌梗死和短期主要不良心血管事件(MACE)的发生率,这可能与其抗炎和抗氧化特性有关。剂量反应荟萃分析预测,在10 - 200mg/kg/d的范围内,200mg/kg/d体重是姜黄素的最佳剂量,根据现有出版物,该剂量安全无毒。我们的研究是首个同时纳入临床前和临床研究的荟萃分析。我们认为,在动物研究中,姜黄素可能在急性心肌梗死中发挥心脏保护作用,主要通过抗氧化、抗炎、抗凋亡和抗纤维化作用。此外,从临床研究中我们发现,姜黄素可能需要更长的疗程和更大的剂量来保护心肌,其疗效主要体现在降低心肌梗死和MACE的发生率上。我们的研究结果为进一步研究提供了一些有意义的建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3474/10034080/138411846cee/fphar-14-1111459-g001.jpg

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