目的 从网络药理学角度探讨麝香治疗脑缺血再灌注损伤的分子机制，并采用动物实验验证。方法 借助TCMID及上海化学专用数据库检索麝香有效成分，利用Swiss Target Prediction数据库预测各成分作用靶点。通过UniProt、GeneCards数据库查询靶点对应的基因，运用Cytoscape V3.6.1构建成分-靶点网络，通过DAVID进行GO功能富集分析和KEGG通路富集分析，预测其作用机制。建立MCAO/R大鼠模型，灌胃麝香及麝香酮治疗后mNSS行为学评分，伊文思蓝法检测血脑屏障通透性，TTC染色检测脑梗塞率，HE染色检测神经元坏死率，荧光定量PCR检测CHRM2、GABBR2、GRM7、HSP90AA1 mRNA 表达。结果 获得麝香大环化合物、甾族化合物及多种氨基酸共17种有效成分，筛选出与脑缺血再灌注损伤交集的靶点107个，并得到神经递质受体活性，血清素受体活性，谷氨酸受体活性等140条生物学过程，KEGG通路富集得到神经活性配体-受体相互作用，谷氨酸能突触等103条信号通路。动物实验结果表明，与假手术组相比，模型组行为学评分、血脑屏障通透性、脑梗塞率、神经元坏死率及CHRM2 mRNA 表达明显升高（P<0.01），GABBR2、GRM7、HSP90AA1 mRNA表达明显降低（P<0.01）。与模型组相比，麝香组与麝香酮组行为学评分、血脑屏障通透性、脑梗塞率、神经元坏死率及CHRM2 mRNA表达均明显降低（P<0.05），麝香组GABBR2、GRM7 mRNA表达明显升高（P<0.01），麝香酮组GABBR2、HSP90AA1 mRNA 表达明显升高（P<0.01）。结论 麝香治疗脑缺血再灌注损伤的机制主要集中在对脑神经递质及受体活性的调节，推测这可能是麝香“醒神开窍”功效的科学内涵，麝香酮可能是该功效的主要活性物质。

Objective To explore the molecular mechanism of musk in the treatment of cerebral ischemia reperfusion injury from the perspective of network pharmacology, and to verify it by animal experiments.Methods The effective components of musk were searched by TCMID and Shanghai Chemical Database, and the targets of each component were predicted by Swiss Target Prediction database. Genes corresponding to targets were searched by UniProt and GeneCards databases, and then the component-target network was constructed by Cytoscape V3.6.1. GO function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID to predict its mechanism. The middle cerebral artery occlusion and reperfusion (MCAO/ R) model was established by suture method. The behavioral score was evaluated after intragastric administration of musk and musk ketone. TTC staining was used to detect the rate of cerebral infarction. HE staining was used to detect the rate of neuronal necrosis. The mRNA expressions of CHRM2, GABBR2, GRM7 and HSP90AA1 were detected by real-time fluorescence quantitative PCR.Results A total of 17 active ingredients were obtained from musk macrocyclic compounds, steroids and multiple amino acids. 107 targets interacting with cerebral ischemia reperfusion injury were screened. 140 biological processes including neurotransmitter receptor activity, serotonin receptor activity and glutamate receptor activity were obtained. The KEGG pathway was enriched and screened to obtain 103 signaling pathways, including neuroactive transient cationic channel inflammatory mediators regulation, and glutamatergic synapses. The results of animal experiments showed that compared with the sham operation group, the behavioral score, cerebral infarction rate, neuronal necrosis rate and CHRM2 mRNA expression in the model group were significantly increased (P<0.01), and the mRNA expressions of GABBR2, GRM7 and HSP90AA1 were significantly decreased (P<0.01). Compared with the model group, the behavioral score, cerebral infarction rate, neuronal necrosis rate and CHRM2 mRNA expression in the musk group and the musk ketone group were significantly decreased (P<0.05). The mRNA expressions of GABBR2 and GRM7 in the musk group were significantly increased (P<0.01). The mRNA expressions of GABBR2 and HSP90AA1 in the musk ketone group were significantly increased (P<0.01).Conclusion The mechanism of the efficacy of "consciousness-restoring resuscitation" of musk on cerebral ischemia-reperfusion injury mainly focuses on the regulation of brain neurotransmitter and receptor activity. Muscone is an important active component of this efficacy.

山东省自然科学基金委员会重点项目（ZR2020KH003）：人工麝香核心组分——麝香酮及衍生物治疗缺血性中风成药性评价，负责人：韩冰冰；济南市高校院所创新团队项目（2020GXRC012）：中医防治脑卒中活血化瘀类经典名方研究，负责人：王世军；山东省高等学校青创科技支持计划（2019KJK013）：治疗脑病中医经典名方研究创新团队，负责人：王媛。