血府逐瘀胶囊对心肌梗死的影响：网络药理学与实验验证

Effect of Xuefu Zhuyu Capsule on Myocardial Infarction: Network Pharmacology and Experimental Verification.

作者信息

Duan Jinlong, Lin Jianguo, Zhang Nixue, Wang Qingqing, Li Na, Yao Kuiwu

机构信息

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Evid Based Complement Alternat Med. 2023 Jan 31;2023:5652276. doi: 10.1155/2023/5652276. eCollection 2023.

BACKGROUND

Myocardial infarction (MI) is the most severe manifestation of cardiovascular disease. Xuefu Zhuyu Capsule (XFC), a proprietary Chinese medicine, is widely used in various cardiovascular diseases. At present, the molecular mechanism of XFC remains unclear.

OBJECTIVE

To explore the mechanism of anti-MI effects of XFC by combining network pharmacology and experiments.

METHODS

TCMSP, GeneCards, and DisGeNET databases were used to find the target of XFC. PPI analysis was performed by the STRING database. KEGG and GO analyses were performed by Metascape Database. Molecular docking was performed by Autodock Vina. HE staining, echocardiography, immunofluorescence, and TUNEL were performed to verify the prediction results.

RESULTS

Network pharmacology showed that quercetin, kaempferol, -sitosterol, luteolin, and baicalein were the main active ingredients of XFC. TNF, IL6, TP53, VEGFA, JUN, CASP3, and SIRT1 were the main targets of XFC. KEGG results showed that key genes were mainly enriched in lipid and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and NF-B signaling pathway. HE staining showed that XFC could improve the morphology of myocardial tissue. Echocardiography showed that XFC could improve cardiac function. TUNEL showed that XFC could reduce cardiomyocyte apoptosis. Immunofluorescence showed that XFC could reduce the expression of -smooth muscle actin (-SMA) and increase the expression of CD31. In addition, we found that XFC may exert its therapeutic effects through SIRT1.

CONCLUSION

This study demonstrated that SIRT1 may be the target of XFC in the treatment of MI. The active ingredients of XFC and SIRT1 can be stably bound. XFC could inhibit apoptosis, promote angiogenesis, and improve myocardial fibrosis through SIRT1.

背景

心肌梗死（MI）是心血管疾病最严重的表现形式。血府逐瘀胶囊（XFC）作为一种中成药，广泛应用于各种心血管疾病的治疗。目前，血府逐瘀胶囊的分子机制尚不清楚。

目的

通过网络药理学与实验相结合的方法，探讨血府逐瘀胶囊抗心肌梗死作用的机制。

方法

利用中药系统药理学数据库与分析平台（TCMSP）、基因卡片（GeneCards）和疾病基因数据库（DisGeNET）查找血府逐瘀胶囊的作用靶点。通过STRING数据库进行蛋白质-蛋白质相互作用（PPI）分析。利用Metascape数据库进行京都基因与基因组百科全书（KEGG）和基因本体（GO）分析。通过Autodock Vina进行分子对接。采用苏木精-伊红（HE）染色、超声心动图、免疫荧光和末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）验证预测结果。

结果

网络药理学研究表明，槲皮素、山柰酚、β-谷甾醇、木犀草素和黄芩苷是血府逐瘀胶囊的主要活性成分。肿瘤坏死因子（TNF）、白细胞介素-6（IL6）、肿瘤蛋白p53（TP53）、血管内皮生长因子A（VEGFA）、原癌基因蛋白c-Jun（JUN）、半胱天冬酶3（CASP3）和沉默信息调节因子1（SIRT1）是血府逐瘀胶囊的主要作用靶点。KEGG结果显示，关键基因主要富集于脂质与动脉粥样硬化、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路和核因子-κB（NF-κB）信号通路。HE染色显示，血府逐瘀胶囊可改善心肌组织形态。超声心动图显示，血府逐瘀胶囊可改善心脏功能。TUNEL结果显示，血府逐瘀胶囊可减少心肌细胞凋亡。免疫荧光显示，血府逐瘀胶囊可降低α-平滑肌肌动蛋白（α-SMA）的表达，增加血小板内皮细胞黏附分子-1（CD31）的表达。此外，我们发现血府逐瘀胶囊可能通过SIRT1发挥其治疗作用。