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[摘要]
目的 用计算机网络药理学技术分析柴胡疏肝散治疗卒中后抑郁的有效成分,并预测其作用机制。方法 从中药系统药理学分析平台(TCMSP)中获取柴胡疏肝散的化学成分和靶点,同时利用OMIM、TTD和PharmGkb数据库获取治疗卒中和抑郁的共有靶标。采用Excel筛选分子和靶标,Cytoscape软件建立柴胡疏肝散的中药成分-靶点网络图,通过生物学信息注释数据库(DAVID)对基因功能及代谢通路进行分析。结果 从数据库筛选出柴胡疏肝散122个中药成分与卒中后抑郁的42个靶蛋白相互作用,其中雌激素受体(ESR1)、前列素内环氧化物合成酶2(PTGS2)、糖原合成酶激酶3β(GSK3β)、SLC6A4和白三烯A4水解酶(LTA4H)为柴胡疏肝散治疗卒中后抑郁的作用靶点,主要涉及花生四烯酸代谢通路、5-羟色胺能突触通路、催乳素信号通路和甲状腺激素信号通路,通过调节炎症应答、突触合成、雌激素应答、记忆、生物合成、药物反应和昼夜节律从而治疗卒中后抑郁。结论 通过网络药理学研究揭示了柴胡疏肝散治疗卒中后抑郁的可能机制,为进一步阐明其作用靶点奠定了基础。
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[Abstract]
Objective To assess the effective components of Chaihu Shugan Powder in the treatment of post-stroke depression and its potential mechanisms. Methods The chemical constituents and targets of Chaihu Shugan Powder were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Common targets for stroke and depression were obtained from OMIM, TTD, and PharmGkb databases. Excel was used to filter molecules and targets, so as the Cytoscape software to establish the network between Chinese medicine molecules and target. The biological information annotation database was used to analyze gene function and metabolic pathway. Results There were 122 Chinese medicine ingredients from databases mteracting with 42 target proteins of post-stroke depression. Finally, five targets including Estrogen receptor (ESR1), prostaglandin G/H synthase 2 (PTGS2), glycogen synthase kinase-3 beta (GSK3β), sodium-dependent dopamine transporter (SLC6A4), and leukotriene A-4 hydrolase (LTA4H) were selected as the action targets for treating post-stroke depression, involved the arachidonic acid metabolism, 5-serotonin ergic synaptic pathway, prolactin signaling pathway, and thyroid hormone signaling pathways, which can treat post-stroke depression by regulating inflammatory response, synapse synthesis, estrogen response, recollection, biosynthesis, drug reaction, and circadian rhythm.Conclusion The network pharmacology study revealed the underlying mechanisms of Chaihu Shugan Powder for treating the post-stroke depression.
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[基金项目]
江苏省中医药局科技项目(YB2015052);江苏省卫生计生委科研课题(Z201504);南京中医药大学重点学科项目;江苏省第二中医院院内课题(SEZJJZ201601)