基于 PI3K-AKT 通路研究联合辅酶 Q10 治疗心力衰竭的作用机制。
Investigating the Mechanism of Action of Combined with Coenzyme Q10 in the Treatment of Heart Failure Based on PI3K-AKT Pathway.
机构信息
Department of Pharmaceutics, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, People's Republic of China.
Shaanxi Dongtai Pharmaceutical Co., Ltd, Shaanxi, People's Republic of China.
出版信息
Drug Des Devel Ther. 2023 Mar 27;17:939-957. doi: 10.2147/DDDT.S393995. eCollection 2023.
PURPOSE
To study the active components, drug targets and mechanism of () combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF).
METHODS
Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot.
RESULTS
Network pharmacology combined with experimental validation suggests that the mechanism of action of combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1β and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of and CQ10 was more effective compared with CQ10 alone, ie, the ability of combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway.
CONCLUSION
The therapeutic effect of combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.
目的
研究（）与辅酶 Q10（CQ10）联合治疗心力衰竭（HF）的活性成分、药物靶点和作用机制。
方法
采用网络药理学结合基因表达综合芯片法分析（）与 CQ10 联合作用治疗心力衰竭的主要通路，随后采用分子对接技术验证主要通路关键蛋白及其相应化合物的生物活性，最后采用盐酸异丙肾上腺素诱导大鼠心力衰竭模型，通过苏木精-伊红染色、TUNEL、免疫组织化学和 Western blot 验证（）与 CQ10 联合治疗心力衰竭的分子机制。
结果
网络药理学结合实验验证表明，（）与 CQ10 联合治疗心力衰竭的作用机制可能涉及 CQ10、柠檬醛、五味子丙素、五味子乙素、戈米辛 O、五味子醇 C 等成分，可能协同抑制 PI3K-AKT 信号通路，影响该通路中 AKT1、PIK3CG 等靶点的表达。此外，（）与 CQ10 联合应用可有效改善心力衰竭大鼠的心脏系数，减少心肌纤维化面积，降低心力衰竭大鼠血清中白细胞介素-1β和肿瘤坏死因子-α的水平，减少心肌细胞凋亡，增加 Bcl-2 的表达，降低心肌组织中 p-PI3K/PI3K、p-AKT/AKT、P65 和 Bax 的表达。结果比较表明，（）与 CQ10 联合应用的效果优于 CQ10 单独应用，即（）与 CQ10 联合改善心功能、抑制心肌细胞凋亡和减轻炎症反应的能力在于 PI3K/AKT 信号通路的协同作用。
结论
（）与 CQ10 联合治疗心力衰竭的疗效可能通过抑制 PI3K/AKT 信号通路发挥作用。
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