基于气血理论探讨芪参益气滴丸调控eNOS-NO/cGMP/PKG通路干预射血分数保留心衰的分子机制

Heart failure with preserved ejection fraction (HFpEF) has attracted much attention in recent years. Early intervention of HFpEF is crucial for delaying the deterioration of heart function. However, there is still no effective treatment for HFpEF in Western medicine. According to Traditional Chinese Medcine, the pathogenesis of HFpEF is qi-deficiency, blood-stasis and water-retention. Benefiting qi for activating blood circulation is the effective treatment for HFpEF and Qishen Yiqi dropping pill (QSYQ) is the typical compound. Modern medical research showed that HFpEF is closely related to the inflammation caused by oxidative stress and the eNOS-NO/cGMP/PKG pathway palys a key role in the pathophysiological process. QSYQ has antioxidant and anti-inflammatory effects and its pleiotropic effect has attracted international attention. Therefore, we hypothesize that QSYQ can inhibit myocardial oxidative stress and inflammatory reaction by regulating eNOS-NO/cGMP/PKG pathway, improve myocardial compliance and reduce stiffness, and thus play the role of treating HFpEF. In this study, we investigate the effect of QSYQ on inhibiting myocardial hypertrophy and interstitial fibrosis, improving diastolic function in HFpEF rats. We also explore its molecular mechanism of antioxidant and anti-inflammatory through eNOS-NO/cGMP/PKG pathway. The results may help to provide new ideas for the prevention and treatment of HFpEF and has practical significance in the protection of cardiac function in the early prevention and treatment of heart failure.

射血分数保留心衰（HFpEF）近年来备受关注，气血理论认为与射血分数降低心衰的阳虚不得温化水饮的病机不同，HFpEF病机为气虚血瘀终致水停，治疗应以益气活血为法，芪参益气滴丸益气活血通脉，是以气血理论为指导的代表方。并且HFpEF与氧化应激所致的炎性反应密切相关，eNOS-NO/cGMP/PKG通路是上述反应的关键通路，芪参益气滴丸具有抗氧化抗炎的效应，其生物多效性引起国际广泛关注。基于此，本研究提出体现气血理论的芪参益气滴丸是否能通过调控eNOS-NO/cGMP/PKG通路抑制心肌氧化应激及炎性反应，改善心肌顺应性及僵硬度，从而发挥干预HFpEF的作用？以eNOS-NO/cGMP/PKG通路为切入点，观察芪参益气滴丸对大鼠心脏舒张功能、心肌僵硬度及eNOS、cGMP、PKG-I、IL-6、TNF-α等表达的影响，探讨其抑制心肌氧化应激及炎性反应的分子机制，以期为HFpEF的防治提供新思路

如何早期干预射血分数保留心衰是临床亟待解决的难题，抑制心肌氧化应激致炎性反应可望成为解决射血分数保留心衰难题的突破口。eNOS-NO/cGMP/PKG 信号通路是射血分数保留心衰氧化应激致炎性反应的关键通路，芪参益气滴丸作为益气活血的代表方药，有明显的抗炎及抗氧化应激的作用，本课题结合中医对于舒张性心衰气虚血瘀的病机认识，为舒张性心衰的防治提供了新的思路。.本课题借助高糖高脂饮食喂养的F344大鼠构建实验模型，阐释了芪参益气滴丸对心功能、氧化应激、炎性因子及eNOS-NO/cGMP/PKG 通路分子的影响，探讨其抑制心肌氧化应激致炎性反应干预射血分数保留心衰的作用通路及分子机制。研究结果表明通过高糖高脂饮食喂养，诱发F344大鼠炎症及氧化应激反应，进一步诱发HFpEF，同时高糖高脂饮食还可促进大鼠衰老的发生。芪参益气滴丸可以通过抑制炎症及氧化应激反应，延缓HFpEF的进程，其机制可能与影响eNOS-NO/cGMP/PKG通路有关。