背景:卒中是全球死亡和残疾的主要原因。目前,通过再灌注治疗急性缺血性中风提出了几个挑战,提高了对保护缺血性半影的补充选择的必要性。最近的调查表明,某些表观遗传因素,具体来说,组蛋白脱乙酰酶(HDAC)和去乙酰化酶,可能有希望用于缺血性中风治疗,最近的研究表明,HDACs或沉默调节蛋白的抑制剂可能在缺血性卒中后提供神经元保护。然而,特定HDAC/沉默调节蛋白亚型对卒中后神经元细胞存活的影响仍不确定.本研究旨在全面概述HDAC及其调节剂在治疗急性缺血性中风中的功能。
方法:本系统综述和荟萃分析将包括动物干预研究,探讨HDAC和沉默调节蛋白在缺血性卒中急性期的疗效。审查将根据系统审查和荟萃分析指南的首选报告项目进行报告。电子搜索将在PubMed进行,WebofScience和Scopus,随后由独立审核员根据既定的资格标准进行筛选。方法学质量将使用SYRCLE偏倚风险工具进行评估。主要结果是梗死体积和功能反应,次要结果建立了先验。与梗死体积有关的数据将用于随机效应荟萃分析。此外,将对功能反应和次要结局进行描述性总结.
结论:迄今为止,尚未对通过HDAC调节治疗缺血性卒中进行系统评价和荟萃分析。对有关临床前研究的现有文献进行全面分析,可以在辨别最有效的试验和临床前研究的进一步标准化方面产生宝贵的见解。
背景:该系统评价已记录在国际前瞻性系统评价登记册(PROSPERO)中,与分配的参考编号:CRD42023381420。
BACKGROUND: Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.
METHODS: This systematic
review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The
review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes.
CONCLUSIONS: No systematic
review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.
BACKGROUND: This systematic
review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420.