基于网络药理学方法及动物实验验证探讨天麻-丹参药对治疗高血压的作用机制。方法（1）通过 TCMSP、BATMAN 及TCMIP 数据库筛选天麻-丹参药对活性成分及其作用靶点；通过Drugbank、Genecard、 TTD、Disgenet 数据库检索获得高血压疾病相关靶点；对药对的活性成分作用靶点与高血压疾病相关靶点取交 集（共同靶点），所得交集靶点即为天麻-丹参药对治疗高血压的潜在作用靶点。将天麻-丹参药对活性成分及其 作用靶点导入Cytoscape 3.9.1 软件，构建“中药-活性成分-靶点”网络，筛选关键活性成分；构建潜在作用靶 点的蛋白互作（PPI）网络，筛选潜在核心靶点；使用Metascape 平台对潜在作用靶点进行GO 功能及KEGG 通路 富集分析。选择关键活性成分与潜在核心靶点进行分子对接验证。（2）将30 只雄性自发性高血压大鼠（SHR）随 机分为模型组、西药组（坎地沙坦酯，0.72 mg·kg-1）及天麻-丹参药对低、中、高剂量组（2.25、4.50、9.00 g·kg-1）， 另选雄性WKY 大鼠为空白组，每组6 只，每日1 次，连续灌胃给药8 周。分别在给药前及药物干预2、4、6、8 周 后检测大鼠尾动脉收缩压；采用HE 染色法观察胸主动脉组织病理变化；Western Blot 法检测腹主动脉中 GRP78、CHOP、Caspase-12 蛋白表达水平。结果（1）共得到天麻-丹参药对活性成分83 个，筛选出天麻-丹 参药对治疗高血压的潜在作用靶点（交集靶点）158 个；5 个关键活性成分：对羟基苯甲酸、4-羟基苄胺、丹参 酮Ⅰ、丹参酮、γ-谷甾醇；6 个潜在核心靶点：IL6、TNF、CASP3、JUN、PTGS2、IL1B；GO 功能富集分析得 到1 826 条生物学过程条目、89 条细胞组分条目、199 条分子功能条目；KEGG 通路富集分析获得186 条通路， 主要涉及神经活性配体-受体相互作用、钙信号通路、炎症应答（如TNF 和MAPK 信号通路）、血管保护（如 HIF-1 和cAMP 信号通路）、氧化应激（如PI3K-Akt 信号通路）等信号通路；丹参酮Ⅰ、丹参酮对6 个潜在核心 靶点均有较强的结合力，γ-谷甾醇对IL6、CASP3、JUN、PTGS2、IL1B 具有较强的结合力。（2）与空白组比较， 模型组大鼠的收缩压显著升高（P＜0.01）；胸主动脉内皮损伤明显，内皮细胞形态异常，可见肿胀、脱落细胞， 组织内膜排序紊乱，内膜结构不完整，出现内膜增厚；腹主动脉中GRP78、CHOP、Caspase-12 蛋白表达量显 著升高（P＜0.01）。与模型组比较，给药组大鼠的收缩压均显著下降（P＜0.01）；胸主动脉损伤减轻，内皮细胞 形态、内膜结构及厚度等均得到不同程度改善；腹主动脉中GRP78、CHOP、Caspase-12 蛋白表达量显著降低 （P＜0.01）。结论天麻-丹参药对可能是通过对羟基苯甲酸、丹参酮、γ-谷甾醇等关键活性成分，作用于 IL6、TNF、CASP3、JUN、PTGS2、IL1B 等核心靶点，调控TNF 信号通路、MAPK 信号通路、PI3K-Akt 信号 通路、PERK 信号通路等关键信号通路，发挥改善血管内皮功能障碍、抑制内质网应激及降血压的作用。

To investigate the mechanism of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair in the treatment of hypertension based on the network pharmacology method and animal experiment verification. Methods （1） TCMSP，BATMAN and TCMIP databases were used to screen the active components and targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair. The hypertension-related targets were obtained by searching the Drugbank， Genecard， TTD and Disgenet databases. The intersection （common target） of the active component target and the target related to hypertension disease was taken， and the obtained intersection target was the potential target of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair for the treatment of hypertension. The active ingredients and their targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair were imported into Cytoscape 3.9.1 software to construct a 'Chinese medicines-active ingredients-targets' network and screen key active ingredients. The protein-protein interaction （PPI） network of potential targets was constructed to screen potential core targets. The Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets. The key active components and potential core targets were selected for molecular docking verification. （2）Thirty male spontaneously hypertensive rats （SHR） were randomly divided into model group， western medicine group （Candesartan Cilexetil， 0.72 mg·kg-1） and low-， medium- and high- dose groups of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma （2.25， 4.50， 9.00 g·kg-1）. Another male WKY rats were selected as blank group，with 6 rats in each group，once a day for 8 weeks. The systolic blood pressure of rat tail artery was detected before administration and 2，4，6 and 8 weeks after drug intervention. The pathological changes of thoracic aorta were observed by HE staining. The protein expression levels of GRP78， CHOP and Caspase-12 in aorta abdominalis were detected by Western Blot. Results （1）A total of 83 active components of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma were obtained，and 158 potential targets （intersection targets） for the treatment of hypertension were screened out. Five key active ingredients：phydroxybenzoic acid， 4-hydroxybenzylamine， tanshinone I， tanshinone， γ - sitosterol； 6 potential core targets： IL6， TNF， CASP3， JUN， PTGS2， IL1B； GO functional enrichment analysis obtained 1 826 biological process items， 89 cell component items， and 199 molecular function items. KEGG pathway enrichment analysis obtained 186 pathways， mainly involving neuroactive ligand-receptor interaction， calcium signaling pathway， inflammatory response （such as TNF and MAPK signaling pathway）， vascular protection （such as HIF-1 and cAMP signaling pathway），oxidative stress （such as PI3K-Akt signaling pathway） and other signaling pathways. Tanshinone I and tanshinone had strong binding force to 6 potential core targets， and γ-sitosterol had strong binding force to IL6， CASP3， JUN， PTGS2 and IL1B. （2） Compared with the blank group， the systolic blood pressure of the model group was significantly increased （P＜0.01） . The thoracic aortic endothelial injury was obvious， the endothelial cell morphology was abnormal，swelling and exfoliated cells could be seen，the intima of the tissue was disordered， the intima structure was incomplete，and the intima was thickened. The protein expressions of GRP78，CHOP and Caspase - 12 in abdominal aorta were significantly increased （P＜0.01） . Compared with the model group， the systolic blood pressure of the rats in the administration group was significantly decreased （P＜0.01）；the injury of thoracic aorta was alleviated，and the morphology，intima structure and thickness of endothelial cells were improved to varying degrees. The protein expressions of GRP78，CHOP and Caspase-12 in abdominal aorta were significantly decreased （P＜0.01） . Conclusion Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair may act on core targets such as IL6，TNF，CASP3，JUN，PTGS2，and IL1B through key active components such as phydroxybenzoic acid， tanshinone， and γ-sitosterol， and regulate key signaling pathways such as TNF signaling pathway，MAPK signaling pathway，PI3K-Akt signaling pathway，and PERK signaling pathway to improve vascular endothelial dysfunction，inhibit endoplasmic reticulum stress，and lower blood pressure

R285.5；R857.3

湖南省自然科学基金项目（2019JJ80114）；湖南省科技厅普惠性政策与创新环境建设计划项目（2021SK51007）；第五批全国中医临床优 秀人才研修项目（国中医药人教函〔2022〕1号）。