Aims. Myocardial reperfusion damage after severe ischemia was an important issue during a clinical practice. However, the exacted pathogenesis involved remained unclear and also lacks effective interventions. Melatonin was identified to exert protective effects for alleviating the myocardial I/R injury. This meta-analysis was determined to evaluate the efficacy of melatonin treatment against reperfusion insult and further summarize potential molecular and cellular mechanisms. Methods and Results. 15 eligible studies with 211 animals (108 received melatonin and 103 received vehicle) were included after searching the databases of PubMed, MEDLINE, Embase, and Cochrane. Pretreatment with melatonin was associated with a significant lower infarct size in comparison with vehicle in myocardial I/R damage (WMD: -20.45, 95% CI: -25.43 to -15.47, ; , ). Evidence from subgroup analyses and sensitivity analysis indicated the robust and consistent cardioprotective effect of melatonin, while the metaregression also did not unmask any significant interactions between the pooled estimates and covariates (i.e., sample size, state, species, study type, route of administration, and duration of reperfusion, along with timing regimen of pretreatment). Accordingly, melatonin evidently increased EF (WMD: 17.19, 95% CI: 11.08 to 23.29, ; , ) and FS (WMD: 14.18, 95% CI: 11.22 to 17.15, ; , ) in the setting of reperfusion damage. Conclusions. Melatonin preadministration conferred a profound cardioprotection against myocardial I/R injury in preclinical studies.

中文翻译：

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褪黑激素对抗心肌缺血再灌注损伤：来自动物研究的荟萃分析和机制洞察。

目标。严重缺血后的心肌再灌注损伤是临床实践中的一个重要问题。然而，所涉及的确切发病机制仍不清楚，也缺乏有效的干预措施。褪黑激素被确定为减轻心肌 I/R 损伤发挥保护作用。该荟萃分析旨在评估褪黑激素治疗再灌注损伤的功效，并进一步总结潜在的分子和细胞机制。方法和结果. 在搜索了 PubMed、MEDLINE、Embase 和 Cochrane 的数据库后，纳入了 15 项符合条件的研究，其中 211 只动物（108 只接受了褪黑激素，103 只接受了载体）。与载体相比，褪黑激素预处理与心肌 I/R 损伤的梗死面积显着降低相关（WMD：-20.45，95% CI：-25.43 至 -15.47，; , ）。来自亚组分析和敏感性分析的证据表明褪黑激素具有强大且一致的心脏保护作用，而元回归也没有揭示汇总估计值和协变量（即样本量、状态、物种、研究类型、给药途径、和再灌注持续时间，以及预处理的时间方案）。因此，褪黑激素明显增加 EF (WMD: 17.19, 95% CI: 11.08 to 23.29,; , )和 FS (WMD: 14.18, 95% CI: 11.22 to 17.15,; , )在再灌注损伤的情况下。结论。在临床前研究中，褪黑激素预给药对心肌 I/R 损伤具有深远的心脏保护作用。