目的 通过网络药理学结合动物实验探究香青兰改善慢性肾脏疾病（chronic kidney disease，CKD）的作用及机制。方法 通过文献查阅得到香青兰的活性成分，同时采用网络药理学方法获得活性成分和CKD交集靶点，构建“活性成分-靶点-疾病”网络和潜在靶点相互作用网络，并通过度值筛选出核心靶点和核心成分，借助Matescape在线平台对核心靶点进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。建立CKD大鼠模型，给予复方α-酮酸片或香青兰提取物干预28 d，给药结束后取血测定尿素氮和肌酐水平；苏木素-伊红（HE）染色观察各组大鼠肾组织病理变化；Western blotting检测各组大鼠肾组织α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、碳酸酐酶IV（carbonic anhydrase IV，CAIV）、β-连环蛋白（β-catenin）、基质金属蛋白9（matrix metalloprotein 9，MMP9）和纤连蛋白（fibronectin，FN）表达。结果 得到香青兰活性成分61个，相关靶点789个，CKD靶点2 194个，香青兰与CKD交集靶点349个。富集分析结果显示，香青兰可能通过7,4′-二氢黄酮、木犀草素、蓟黄素、木犀草苷、木犀草素-7-葡萄糖醛酸苷等核心成分调节CAIV、MMP9、醛糖还原酶（aldose reductase，AKR1B1）等核心靶点，作用于癌症、脂质和动脉粥样硬化、磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）-蛋白激酶B（protein kinase B，Akt）信号通路等途径防治CKD。动物实验结果显示，与模型组比较，香青兰提取物能够显著降低大鼠血清中尿素氮和肌酐水平（P＜0.05、0.01），改善大鼠肾单位损伤，显著下调肾组织CAIV、α-SMA、MMP9和FN蛋白表达（P＜0.05、0.01），上调β-catenin蛋白表达（P＜0.05）。结论 香青兰通过多成分、多靶点发挥治疗CKD的作用，其主要活性成分可能通过作用于CAIV调控β-catenin、α-SMA、MMP9、FN的表达，从而改善CKD。

Objective To explore the effect and mechanism of Dracocephalum moldavica on chronic kidney disease (CKD) through network pharmacology combined with animal experiments. Methods The active ingredients of D. moldavica were obtained through literature review, the intersection targets of active ingredients and CKD were obtained using network pharmacology. The “active ingredient-target-disease” network and potential target interaction network were constructed, the core targets and core components were screened by degree values. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of core targets were performed using Matescape online platform. CKD rat model was established, Compound α-Ketoacid Tablets or D. moldavica extracts were given for intervention for 28 d. After the end of administration, blood was taken to measure urea nitrogen and creatinine levels; Hematoxylin-eosin (HE) staining was used to observe the pathological changes in renal tissue of rats in each group; Western blotting was used to detect the expressions of α-smooth muscle actin (α-SMA), carbonic anhydrase IV (CAIV), β-catenin, matrix metalloproteinase 9 (MMP9) and fibronectin (FN) in renal tissues of rats in each group. Results A total of 61 active ingredients, 789 related targets, 2 194 CKD targets, and 349 intersecting targets between D. moldavica and CKD were obtained. The enrichment analysis results showed that D. moldavica might regulate CAIV, MMP9, aldose reductase (AKR1B1) and other core targets through 7,4′-dihydroflavone, luteolin, scrophulein, luteolin-7-O-glucoside, luteolin-7-glucuronide and other core components, and act on cancer, lipid and atherosclerosis, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signal pathway and other pathways to prevent CKD. Animal experiment results showed that compared with model group, D. moldavica extract could significantly reduce the levels of urea nitrogen and creatinine in serum of rats (P < 0.05, 0.01), improve nephron damage, significantly down-regulate the protein expressions of CAIV, α-SMA, MMP9 and FN in renal tissue (P < 0.05, 0.01), and up-regulate the protein expression of β-catenin (P < 0.05). Conclusion D. moldavica exerts therapeutic effects on CKD through multiple components and targets, and its main active ingredients may improve CKD by regulating the expressions of β-catenin, α-SMA, MMP9, and FN through CAIV.

R285.5

“天山英才”医药卫生高层次人才培养计划项目（TSYC202301B099）；新疆维吾尔自治区自然科学基金面上项目（2022D01A303）；新疆维吾尔自治区公益性科研院所基本科研业务经费资助项目（KY2022145）