Table6_The synergistic compatibility mechanisms of fuzi against chronic heart failure in animals: A systematic review and meta-analysis.pdf

Background: Fuzi’s compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms.
Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions.
Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dtmax, −dP/dtmax, TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration.
Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo, and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model–effect and time-effect relationships.

背景：附子（Fuzi）与其他药物的配伍是治疗慢性心力衰竭（CHF）的有效手段。临床前动物实验已揭示其多种潜在的协同配伍机制，但相关结果的可靠性与可重复性均不足。为此，本研究针对临床前动物研究开展系统评价与荟萃分析，以整合相关证据，对该配伍方案进行定性与定量评估，并总结潜在的协同作用机制。
方法：在9个在线数据库中全面检索潜在相关研究。筛选标准基于参与者、干预措施、对照、结局指标及研究设计策略。采用SYRCLE动物实验偏倚风险评估工具进行方法学质量评价。依据《Cochrane干预性系统评价手册》，使用RevMan V.5.3与STATA/SE 15.1软件完成荟萃分析。
结果：本系统评价与荟萃分析共纳入24项研究。荟萃分析中共评估12项结局指标，包括B型钠尿肽（BNP）、心率（HR）、心脏重量指数（HWI）、醛固酮（ALD）、左心室舒张末期压（LVEDP）、左心室收缩压（LVSP）、射血分数（EF）、短轴缩短率（FS）、最大左心室压力上升速率（+dP/dtmax）、最大左心室压力下降速率（−dP/dtmax）、肿瘤坏死因子-α（TNF-α）及钠钾-ATP酶（Na+-K+-ATPase）活性。按造模方法与干预时长开展亚组分析。
结论：研究表明，附子配伍用药对慢性心力衰竭模型动物的协同治疗效果优于单用附子，具体体现为心功能改善、抗心室重构与心肌损伤、调节心肌能量代谢紊乱及肾素-血管紧张素-醛固酮系统、减轻炎症反应、改善体内代谢过程、抑制心肌细胞凋亡。慢性心力衰竭造模方法与给药时长的差异，可产生潜在的模型-效应关系与时间-效应关系。