基于SIRT3/FoxO介导的去乙酰化-自噬途径探讨参附益心颗粒改善心衰的作用机制

慢性心力衰竭，是多种心脏疾病的严重和终末阶段，患病率高、死亡率高、再住院率高，经济负担重，已成为严重影响公众健康的心血管疾病。“能量缺乏”是心衰发生、发展的主要因素，线粒体结构异常与功能障碍，是心脏能量失衡的驱动力，目前对慢性心力衰竭的规范治疗，主要依赖于节约能量的手段，疗效确切，但并未解决心肌能量异常的根本原因。SIRT3/FoxO信号通路，能够通过介导去乙酰化调控线粒体自噬，改善线粒体功能，为治疗心衰的有效作用靶点。参附益心颗粒，为我院名老中医治疗心力衰竭的经验方，前期随机、双盲、安慰剂对照试验已证实能够提升心衰患者心功能，网络药理学分析及血清代谢组学检测结果显示，参附益心颗粒干预组乙酰化水平抑制，且与FoxO信号通路强相关，参附益心颗粒改善心功能是否与SIRT3/FoxO介导的去乙酰化-自噬相关，需进一步验证。围绕此假说，本研究从整体动物实验、离体细胞实验两方面进行验证。

Chronic heart failure is a serious and final stage of various heart diseases, with a high prevalence rate, high mortality rate, high readmission rate, and posing a heavy economic burden on the patients. It has become a cardiovascular disease that seriously affects public health. "Energy deficiency" is the main factor for the occurrence and development of heart failure. Mitochondrial structural abnormalities and dysfunction are the driving forces of cardiac energy imbalance. At present, the procedure-based treatment of chronic heart failure mainly relies on energy-saving means, with definite curative effect, but does not solve the root cause of myocardial energy abnormalities. SIRT3/FoxO signaling pathway can regulate mitochondrial autophagy and improve mitochondrial function by mediating deacetylation and is an effective target for the treatment of heart failure. Shenfuyixin Granule is an experience prescription for the treatment of heart failure by renowned and experienced traditional Chinese medicine doctors in our hospital. Previous randomized, double-blind, placebo-controlled trials have proved that they can improve cardiac function in patients with heart failure. The results of network pharmacological analysis and serum metabonomics test show that the acetylation level in the intervention group of Shenfuyixin Granules is inhibited and strongly correlated with FoxO signaling pathway. Whether the improvement of cardiac function by Shenfuyixin Granules is related to SIRT3/FoxO mediated deacetylation-autophagy needs further verification. Around this hypothesis, this study verified it from two aspects, namely, whole animal experiment and in vitro cell experiment.