摘要
背景 脑梗死是由各种原因引起的局部脑组织区域供血障碍,通脑饮为江苏省中医院治疗脑梗死的协定方,但具体作用机制尚不清楚.目的 本研究旨在通过网络药理学和临床试验,解释通脑饮治疗脑梗死的机制.方法 选取 2019 年 1 月—2020 年 6 月江苏省中医院收治的 199 例脑梗死患者.根据随机数字表法,将患者分为对照组(97 例)和试验组(102 例).两组均接受稳定型脑梗死的标准化治疗,试验组加用通脑饮治疗.治疗前和治疗 2 周时,两组均采用美国国立卫生研究院卒中量表(NIHSS)评估卒中引起的功能损害程度,采用改良Rankin量表(mRS)评估神经功能的恢复情况.从TCMSP和文献中筛选通脑饮的化学成分,选择生物利用度(OB)≥30%和药物相似性(DL)≥0.18要求的成分寻找该处方的有效成分.利用OMIM和GeneCards数据库分析通脑饮治疗脑梗死的分子靶点.在筛选出共同靶点后,用Cytoscape软件、String数据库分别绘制化合物和靶蛋白的网络图、构建蛋白相互作用(PPI)网络和基因本体论(GO)功能及京都基因和基因组百科全书(KEGG)信号通路富集分析.最后,进行分子对接实验,确定通脑饮治疗脑梗死的主要活性成分.结果 治疗后,试验组NIHSS、mRS评分均低于对照组(P<0.05).最终得到通脑饮活性成分 60 个,潜在靶点 147 个,疾病相关靶点 5 167 个,药物与疾病的交集靶点 121 个.KEGG信号通路富集分析获得前列腺癌症、神经活性配体-受体相互作用、白介素(IL)-17 信号通路、催乳素信号通路、PI3K-Akt信号通路、钙信号通路等.分子对接显示,通脑饮治疗脑卒中的主要活性成分β谷甾醇、山柰酚和胡萝卜素与核心蛋白雄激素受体(AR)有较好的结合性.结论 通脑饮可能通过激活AR来治疗脑梗死.IL-17 信号通路、PI3K-Akt信号通路和催乳素信号通路也是潜在的机制.
Abstract
Background Cerebral infarction is a disorder of blood supply to the local brain tissue area caused by various causes.Tongnao Decoction is approved and used in Jiangsu Province Hospital of Chinese Medicine for the treatment of cerebral infarction.However,the specific mechanisms underlying its action remain unclear.Objective To explain the mechanism of Tongnao Decoction in the treatment of cerebral infarction through network pharmacology and clinical trails.Methods From January 2019 to June 2020,a total of 199 patients with cerebral infarction admitted to Jiangsu Province Hospital of Chinese Medicine were included in the clinical study.and divided into the control group(97 cases)and experimental group(102 cases)according to the method of random number table.Both groups received standardized treatment for stable cerebral infarction,and the experimental group was treated with Tongnao Decoction.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the degree of functional impairment caused by stroke,and the modified Rankin Scale(mRS)was used to assess the recovery of neurological function for both groups before treatment and at 2 weeks of treatment.The chemical compounds of Tongnao Decoction were screened from TCMSP and literature,and those with bioavailability(OB)≥30%and drug-like properties(DL)≥0.18 requirements were selected to find the active ingredient of the prescription.OMIM and GeneCards databases were used to analyze the molecular targets of Tongnao Decoction for the treatment of cerebral infarction.After screening the common targets,Cytoscape software,String database were used to plot the network of compounds and target proteins,construct protein-protein interaction(PPI)network,gene ontology(GO)function,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,respectively.Molecular docking experiments were finally performed to identify the main active ingredients of Tongnao Decoction for the treatment of cerebral infarction.Results After treatment,the scores of NIHSS and mRS in the experimental group were lower than those in the control group(P<0.05).Finally,60 active ingredients of Tongnao Decoction were obtained,including 147 potential targets,5 167 disease-related targets,and 121 intersection targets of drugs and diseases.The enrichment analysis of KEGG signaling pathway obtained prostate cancer,neuroactive ligand-receptor interaction,IL-17 signaling pathway,prolactin signaling pathway,PI3K-Akt signaling pathway,calcium signaling pathway,etc.Molecular docking showed that β-sitosterol,kastricol and carotene,the main active ingredients of Tongnao Decoction in the treatment of stroke,had good binding properties to the core protein androgen receptor(AR).Conclusion Tongnao Decoction may play a role in treating cerebral infarction by activating AR.IL-17 signaling pathway,PI3K-Akt signaling pathway and prolactin signaling pathway are potential mechanisms as well.
维普
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