目的 基于网络药理学、分子对接和动物实验验证探讨五参汤治疗慢性心力衰竭（CHF）的作用机制。 方法 利用 TCMSP 数据库获取五参汤药物中的活性成分。通过 SwissTargetPrediction 平台及 OMIM、TTD、 DisGeNet、GeneCards 数据库得到五参汤成分及慢性心力衰竭的基因靶点，二者交集靶点为五参汤治疗慢性心 力衰竭的潜在靶点。由 Cytoscape 数据库得到核心靶点，将核心靶点再次计算后筛选得到重要靶点，并构建 “药物-成分-核心靶点”网络及靶点蛋白互作网络（PPI）。以重要靶点在 R 软件上进行 GO 及 KEGG 富集分析。 随后采用分子对接验证主要活性成分与关键通路的靶点的结合水平，并在此基础上进行实验验证。采用小鼠心 肌梗死致慢性心力衰竭模型，利用 B 超、HE、Masson 及 Western Blot 验证实验结果。结果 共收集到有效 药物成分 63 种，成分相关靶点 768 个和疾病靶点 12 933 个，二者交集共 706 个靶点。在 Cytoscape 中计算得 到核心靶点 137 个，其中重要靶点为 28 个。PPI 提示 STAT3、Caspase-3、Bcl2 为治疗过程的关键靶点。GO 及 KEGG 分析显示五参汤治疗慢性心力衰竭可能通过小分子代谢、激素反应、碳水化合物代谢和氧化应激反 应来实现，这些进程可能与 AGE-RAGE 信号通路、PI3K-Akt 信号通路、IL-17 信号通路以及 HIF-1 通路有 关。B 超、HE、MASSON 结果示，与模型组相比，给药组不同程度地缓解了小鼠的心功能障碍及炎症浸润和 纤维化等病理改变。Western Blot 结果显示五参汤能逆转 STAT3、HIF1A、Caspase-3 的高表达（P＜0.05，P＜ 0.01，P＜0.001）以及 Bcl2 的低表达（P＜0.05），从而使慢性心力衰竭得到改善。结论 五参汤可能通过抑制 HIF1A、STAT3、Caspase-3 的蛋白表达，同时增加 Bcl2 的蛋白表达，实现对 HIF-1 通路及凋亡相关信号的调 控发挥对慢性心力衰竭的治疗作用。

Objective To explore the mechanism of Wushen Decoction in the treatment of chronic heart failure （CHF） based on network pharmacology，molecular docking and animal experiments. Methods The active components in Wushen Decoction were obtained by TCMSP database. The SwissTargetPrediction platform and OMIM， TTD， DisGeNet， GeneCards databases were used to obtain the components of Wushen Decoction and the gene targets of chronic heart failure. The intersection of the two targets was the potential target of Wushen Decoction in the treatment of CHF. The core targets were obtained by Cytoscape，among which the important targets were calculated again，and the ‘drugs-components-core targets’network and target PPI were constructed. GO and KEGG enrichment analysis was performed on R with important targets. Subsequently，molecular docking was used to verify the binding level of the main active components to the targets of the key pathways，and experimental verification was performed on this basis. The CHF model induced by myocardial infarction in mice was used to verify the experimental results by B-ultrasound，HE， Masson and Western Blot. Results A total of 63 effective drug components were collected. There were 768 componentrelated targets and 12 933 disease targets，with a total of 706 targets. A total of 137 core targets were calculated in Cytoscape，of which 28 were important targets. PPI suggested that STAT3，Caspase-3 and Bcl2 were the key targets in the treatment process. GO and KEGG analysis showed that the treatment of chronic heart failure with Wushen Decoction may be achieved through small molecule metabolism，hormone response，carbohydrate metabolism and oxidative stress response. These processes may be related to AGE-RAGE signaling pathway， PI3K-Akt signaling pathway， IL-17 signaling pathway and HIF-1 pathway. The results of B-ultrasound，HE and MASSON showed that compared with the model group， the administration group alleviated the pathological changes of cardiac dysfunction， inflammatory infiltration and fibrosis in mice to varying degrees. Western Blot showed that Wushen Decoction could reverse the high expressions of STAT3，HIF1A and Caspase-3 （P＜0.05，P＜0.01，P＜0.001） and the low expression of Bcl2 （P＜ 0.05）， thus improving chronic heart failure. Conclusion Wushen Decoction may inhibit the protein expressions of HIF1A，STAT3 and Caspase-3，and increase the protein expression of Bcl2，so as to preform the regulation of HIF-1 pathway and apoptosis-related signals and play a therapeutic role in CHF.

R285.5

国家自然科学基金面上项目（82074369）