目的 基于网络药理学和实验验证探讨清肝化痰方治疗代谢综合征（MetS）的作用机制。方法 （1）通过 中药系统药理学数据库与分析平台（TCMSP）筛选清肝化痰方的有效成分及其对应的靶点蛋白；采用 GeneCards、OMI、TTD 及 PharmGkb、DrugBank 等数据库检索 MetS 相关疾病靶点。借助 Venny 2.1 在线平台对 药物活性成分靶点与疾病相关靶点取交集，获取清肝化痰方治疗 MetS 的潜在作用靶点。构建“药物-活性成 分-靶点”网络，将共同靶点导入 STRING 11.0 数据库，获取 PPI 网络关系，筛选出清肝化痰方治疗 MetS 的关 键活性成分及核心靶点。运用 Metascape 数据库对共同靶点进行 GO 功能及 KEGG 通路富集分析。（2）采用高脂 饲料饲养复制 MetS 模型。将 40 只 C57BL/6J 小鼠随机分为对照组、模型组及清肝化痰方低剂量组（7.28 g·kg-1 ）、 中剂量组（14.56 g·kg-1 ）、高剂量组（29.12 g·kg-1 ），每组 8 只。灌胃给药，每天 1 次，连续灌胃 4 周。采用胰岛 素耐受试验（ITT）、丙酮酸耐受试验（PTT）检测小鼠胰岛素敏感性及糖异生能力；试剂盒检测小鼠血清甘油三 酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平；ELISA 法检测 小鼠血清白细胞介素 6（IL-6）、白细胞介素 1β（IL-1β）、肿瘤坏死因子 α（TNF-α）炎症因子水平；RT-qPCR 法 检测小鼠肝组织磷脂酰肌醇 3-激酶（PI3K）、蛋白激酶 B（Akt）、IL-1β、TNF-α、IL-6 mRNA 表达。结果 （1）共 筛选出 532 个清肝化痰方治疗 MetS 的潜在作用靶点；排前 6 位的活性成分为甲酸、槲皮素、山柰酚、甘氨酸、 草酸、琥珀酸；核心靶点有 PIK3CA 、Akt1、EGFR、CCND1、SRC 和 MAPK3 等。GO 功能及 KEGG 通路富集 分析显示，这些靶点主要参与了对营养水平的反应、对类固醇激素的反应、对氧气水平的反应等过程，治疗涉 及 PI3K/Akt 等信号通路。（2）与对照组比较，模型组小鼠空腹血糖、血清 TNF-α、IL-6、IL-1β、TG、TC、 LDL-C 水平及肝组织 TNF-α、IL-1β、IL-6、PI3K、Akt mRNA 表达明显升高（P＜0.05，P＜0.01），ITT、PTT 的血糖曲线下面积（AUC）增大（P＜0.05，P＜0.01），血清 HDL-C 水平降低（P＜0.05，P＜0.01）。与模型组比 较，清肝化痰方给药组小鼠空腹血糖、血清 TNF-α、IL-6、IL-1β、TG、TC、LDL-C 水平及肝组织 TNF-α、 IL-1β、IL-6、PI3K、Akt mRNA 表达明显降低（P＜0.05，P＜0.01），ITT、PTT 的 AUC 减小（P＜0.05，P＜ 0.01），血清 HDL-C 水平升高（P＜0.05，P＜0.01）。结论 清肝化痰方中甲酸、槲皮素、山柰酚、甘氨酸、草 酸和琥珀酸等成分可能是通过调节 PI3K/Akt 信号通路改善 MetS 小鼠肝脏炎症反应及糖脂代谢紊乱，从而起到 防治 MetS 的作用。

Objective To explore the mechanism of Qinggan Huatan Formula in treating metabolic syndrome （MetS） based on network pharmacology and experimental validation. Methods （1） The active components of Qinggan Huatan Formula and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. MetS-related targets were retrieved from GeneCards，OMI， TTD， PharmGkb， and DrugBank databases. The intersection of drug-active component-target and disease-related targets was obtained using the Venny 2.1 platform to identify potential therapeutic targets of Qinggan Huatan Formula for MetS. A "drugs-active components-targets" network was constructed，and the common-target were imported into the STRING database to obtain protein-protein interaction （PPI） networks，identifying key active components and core targets of Qinggan Huatan Formula for MetS. GO functional and KEGG pathway enrichment analyses of common targets were performed using the Metascape database. （2） A MetS model was established by feeding C57BL/6J mice a high-fat diet. Forty mice were randomly divided into five groups： control group， model group， low-dose Qinggan Huatan Formula group （7.28 g·kg-1 ），medium-dose Qinggan Huatan Formula group （14.56 g·kg-1 ），and high-dose Qinggan Huatan Formula group （29.12 g·kg-1 ）， with eight mice in each group. The mice were administered the formula by gavage once daily for four weeks. Insulin tolerance test （ITT） and pyruvate tolerance test （PTT） were used to assess ketone metabolism and insulin sensitivity. Serum levels of triglycerides （TG），total cholesterol （TC），low-density lipoprotein cholesterol （LDL-C），and high-density lipoprotein cholesterol （HDL-C）were measured using assay kits. Serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor- α （TNF- α） were detected by ELISA. The mRNA expression of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， IL-1β， TNF- α， and IL-6 in liver tissues was measured by RT-qPCR. Results （1） A total of 532 potential therapeutic targets of Qinggan Huatan Formula for MetS were identified. The top six active components were formic acid， quercetin， kaempferol， glycine， oxalic acid， and succinic acid. Core targets included PIK3CA， Akt1， EGFR， CCND1，SRC，and MAPK3. GO functional and KEGG pathway enrichment analyses revealed that these targets were mainly involved in processes such as response to nutrient levels，response to steroid hormones，and response to oxygen levels，with therapeutic mechanisms involving pathways such as PI3K/Akt. （2） Compared with the control group，the model group showed significantly increased fasting blood glucose，serum TNF-α，IL-6，IL-1β，TG，TC，LDL-C levels，and liver tissue TNF-α，IL-1β，IL-6，PI3K and Akt mRNA expression （P＜0.05，P＜0.01），increased area under the curve （AUC） of ITT and PTT （P＜0.05，P＜0.01），and decreased serum HDL-C levels （P＜0.05， P＜0.01）. Compared with the model group， the Qinggan Huatan Formula treatment groups showed significantly reduced fasting blood glucose，serum TNF- α，IL-6，IL-1β，TG，TC，LDL-C levels，and TNF- α，IL-1β， IL-6，PI3K and Akt mRNA expression in liver tissue （P＜0.05，P＜0.01），decreased AUC of ITT and PTT （P＜ 0.05， P＜0.01）， and increased serum HDL-C levels （P＜0.05， P＜0.01）. Conclusion Components of Qinggan Huatan Formula， such as formic acid， quercetin， kaempferol， glycine， oxalic acid， and succinic acid， may improve hepatic inflammation and glucose-lipid metabolism disorders in MetS mice by regulating the PI3K/Akt signaling pathway，thereby exerting preventive and therapeutic effects on MetS.

R285.5；R259

国家自然科学基金项目（82160891）