目的 通过超高效液相色谱-四级杆/轨道肼高分辨质谱（UPLC-Q-Qrbitrap HRMS）技术和整合网络药理学，探究苗药芪胶升白胶囊治疗白细胞减少症的作用机制。方法 将18只大鼠随机数字表法分为空白组和实验组，每组9只。空白组ig蒸馏水1 mL，实验组ig芪胶升白胶囊混悬液1 mL（取芪胶升白胶囊的内容物，用蒸馏水超声溶解成混悬液），剂量为2.0 g/kg，连续给药3 d，末次给药剂量为4.0 g/kg。末次给药后，用1%的戊巴比妥钠40 mg/kg麻醉大鼠，于15、30、60、120、240 min从大鼠眼眶静脉丛和尾静脉交替取血，采集含药血清和空白血清；运用UPLC-Q-Qrbitrap HRMS技术定性检测芪胶升白胶囊胶囊成分、含药血清成分和空白血清成分，比对分析得到芪胶升白胶囊的入血成分，再对入血成分构建网络药理学分析模型，通过成分拓扑分析、蛋白相互作用网络（PPI）分析和通路富集分析，得到芪胶升白胶囊的关键成分、关键靶点和富集通路。结果 检测出芪胶升白胶囊中的成分51种，包括淫羊藿苷、苦参碱、槲皮素等；入血成分58种，其中原型入血成分17种，代谢成分41种，包括金雀异黄酮、槲皮素、5,6,7-三甲氧基香豆素、碳环素、脱水淫羊藿素、亚油酸、咖啡酸等；网络药理学分析得到入血成分的靶点基因959个、白细胞减少症的靶点基因3 346个，交集靶点404个， PPI分析预测出蛋白酪氨酸性磷酸非受体型11（PTPN11）、淋巴细胞特异蛋白酪氨酸激酶（LCK）、信号转导及转录激活蛋白3（STAT3）、磷脂酰肌醇-3-激酶催化亚基α（PIK3CA）、磷脂酰肌醇3-激酶调节亚基1（PIK3R1）等核心靶点，通路富集分析发现芪胶升白胶囊可以通过磷脂酰肌醇-3-羟激酶（PI3K）-蛋白激酶B（Akt）、脂质与动脉粥样硬化、Janus激酶/信号转导与转录激活子（JAK-STAT）、叉头框蛋白O（FoxO）、造血细胞谱系、亚油酸代谢等信号通路防治白细胞减少症。结论 明确了芪胶升白胶囊的胶囊成分和入血成分，探究了芪胶升白胶囊可通过多个核心靶点作用于PI3K-AKT、脂质与动脉粥样硬化、JAK-STAT等多条通路来治疗白细胞减少症，为进一步研究苗药芪胶升白胶囊的物质基础和深入阐明其作用机制提供了理论依据。

Objective To explore the material basis and mechanism of the Qijiao Shengbai Capsules in treatment of leukopenia by using UPLC-Q-Qrbitrap HRMS and network pharmacology. Methods A total of 18 rats were randomly divided into blank group and experimental group with 9 rats in each group. The blank group was given 1 mL distilled water intragastrically, and the experimental group received 1 mL of Qijiao Shengbai Capsules suspension intragastrically (the contents of Qijiao Shengbai Capsules were taken and ultrasonically dissolved into suspension with distilled water), the dose was 2.0 g/kg, and the dose was 4.0 g/kg for 3 consecutive days. After the last administration, the rats were anesthetized with 1% pentobarbital sodium 40 mg/kg. At 15, 30, 60, 120, and 240 min, blood was taken alternately from the orbital venous plexus and the caudal vein. The drug-containing serum and blank serum were collected, and the UPLC-Q-Qrbitrap HRMS technology was used to qualitatively detect the Qijiao Shengbai Capsules components, drug-containing serum components, and blank serum components of Qijiao Shengbai Capsules. The blood entry components of Qijiao Shengbai Capsules were obtained by comparative analysis, and the network pharmacological analysis model was constructed for the blood entry components. Through component topology analysis, protein interaction network (PPI) analysis and pathway enrichment analysis, the key components, key targets and enrichment pathway of Qijiao Shengbai Capsules were obtained. Results 51 Main components of Qijiao Shengbai Capsules were identified, including icariin, matrine, quercetin, etc. There were 58 blood components, including 17 prototypical blood components and 41 metabolic components, including genistein, quercetin, 5,6, 7-trimethoxycoumarin, carbaprostacyclin, icaritin, linoleic acid, caffeic acid , etc. Network pharmacological analysis revealed 959 target genes for blood entry components, 3 346 target genes for leukopenia, and 404 intersection targets. PPI analysis predicted the core targets of PTPN11, LCK, STAT3, PIK3CA, PIK3R1, etc. Pathway enrichment analysis showed that Qijiao Shengbai Capsules could be regulated by PI3K-Akt, lipid and atherosclerosis, JAK-STAT, FoxO, hematopoietic cell lineage, and linoleic acid metabolism and other signaling pathways to prevent leukopenia. Conclusion The capsule composition and blood entry composition of Qijiao Shengbai Capsules were clarified, and it was explored that Qijiao Shengbai Capsules could treat leukopenia by acting on PI3K-Akt, lipid and atherosclerosis, JAK-STAT and other pathways through multiple core targets, which provided a theoretical basis for further research on the material basis of Qijiao Shengbai Capsules and further elucidate its mechanism of action.

R285

国家重点研发计划项目（2020YFC2005005）