目的 利用网络药理学，汇总和分析芪参胶囊治疗慢性稳定型心绞痛（SAP）的作用通路、成分和靶蛋白之间的相互作用，并在蛋白质水平上进行验证。为后续芪参胶囊活性成分治疗SAP的深入药理机制研究和临床应用提供研究依据。方法 基于中药系统药理学数据库与分析平台（TCMSP）筛选芪参胶囊活性成分作用靶点，结合GeneCards和OMIM数据库获取相关靶点，构建蛋白互作网络筛选核心靶点，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。建立SAP大鼠模型，给予药物干预14 d后，Western blotting检验大鼠相关通路的蛋白表达。并进行大鼠心功能检测和心脏苏木精-伊红（HE）染色验证芪参胶囊药效。结果 结果共筛选49个成分，296个靶点，进一步筛选得到白细胞介素-6(IL-6)、肿瘤坏死因子（TNF）-α和白蛋白（ALB）为治疗SAP的主要靶点。GO和KEGG分析结果提示芪参胶囊治疗SAP的潜在靶点主要集中在脂质和动脉粥样硬化、凋亡、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)、肿瘤坏死因子（TNF）、缺氧诱导因子-1(HIF-1)等信号通路。Western blotting实验结果显示，与对照组相比，模型组的p-PI3K/PI3K、pAkt/Akt总蛋白表达显著低于对照组（P<0.05）;p-STAT3/STAT3总蛋白表达显著高于对照组（P<0.05）。给药后，芪参胶囊中、高剂量较模型组的p-PI3K/PI3K总蛋白表达显著升高（P<0.05）；芪参胶囊高剂量组p-Akt/Akt总蛋白表达显著升高（P<0.01）；芪参胶囊高剂量组p-STAT3/STAT3总蛋白表达显著降低（P<0.05）。结论 芪参胶囊可能通过激活PI3K/Akt通路发挥心肌保护作用。

Objective To summarize and analyze the interaction among the action pathways, components and target proteins of Qishen Capsules in the treatment of chronic stable angina pectoris(SAP) using network pharmacology, and to verify it at the protein level. To provide research basis for the in-depth pharmacological mechanism study and clinical application of the active ingredients of Qishen Capsules in the treatment of SAP in the future. Methods Based on the Traditional Chinese Medicine Systems Pharmacology(TCMSP) database, the active ingredient action targets of Qishen Capsules were screened. Combined with the GeneCards and OMIM databases to obtain relevant targets, a protein-protein interaction network was constructed to screen core targets. Gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted. A SAP rat model was established. After 14 d of drug intervention, Western blotting was used to test the protein expression of related pathways in rats. Rat cardiac function tests and cardiac HE staining were conducted to verify the efficacy of Qishen Capsules. Result A total of 49 components and 296 targets were screened. Further screening revealed that interleukin-6(IL-6), tumor necrosis factor(TNF)-α and albumin(ALB) were the main targets for the treatment of SAP. The results of GO and KEGG analyses suggested that the potential targets of Qishen Capsules in the treatment of SAP were mainly concentrated on lipid and signaling pathways such as atherosclerosis, apoptosis, PI3K-Akt, TNF, and HIF-1. The results of Western blotting showed that, compared with the sham group, the total protein expressions of p-PI3K/PI3K and p-Akt/Akt in the model group were significantly lower than those in the sham group(P < 0.05); The total protein expression of p-STAT3/STAT3 was significantly higher than that in the sham group(P < 0.05). After administration, the total protein expression of p-PI3K/PI3K in the medium and high doses was significantly increased compared with the model group(P < 0.05); The total protein expression of p-Akt/Akt in the high-dose group was significantly increased(P < 0.01); The total protein expression of p-STAT3/STAT3 in the high-dose group was significantly decreased(P < 0.05). The results showed that the medium and high-dose groups of Qishen Capsules could significantly improve the cardiac function of rats and alleviate myocardial cell lesions, etc. Conclusion The results suggest that Qishen Capsules may exert myocardial protective effects by activating the PI3K/Akt pathway.

R285.5