首页|基于网络药理学研究清热化痰通腑方治疗缺血性脑卒中的机制

基于网络药理学研究清热化痰通腑方治疗缺血性脑卒中的机制

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目的:基于网络药理学与动物实验验证探讨清热化痰通腑方(HTF)治疗缺血性脑卒中(IS)的潜在作用机制。方法:通过TCMSP、BATMAN筛选HTF的活性成分,预测活性成分的潜在靶点;GeneCards、OMIM、TTD、Drugbank筛选疾病相关靶点;String数据库获得蛋白互作关系;Metascape对关键靶点进行GO和KEGG富集分析。构建动物模型进行实验验证,采用神经功能评分、2,3,5-氯化三苯基四氮唑(TTC)染色、苏木精—伊红(HE)染色、尼氏(Nissl)染色、脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色以及免疫组化等方法验证网络药理学富集结果。结果:通过网络药理学分析,预测到主要的活性成分为芹菜素、槲皮素、山奈酚、β-谷甾醇等;作用于丝氨酸/苏氨酸激酶1(AKT1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、转化相关蛋白53(TP53)等潜在靶点,涉及到的关键通路有脂质和动脉粥样硬化、MAPK信号通路、PI3K-Akt信号通路、TNF信号通路、IL-17信号通路、缺氧诱导因子-1(HIF-1)信号传导途径等。实验结果显示HTF能显著降低脑缺血再灌注大鼠神经功能评分与脑梗死率(P<0。05),能提高神经元存活率(P<0。05),显著降低细胞凋亡率(P<0。05)。结论:基于网络药理学与动物实验验证,发现HTF通过多成分作用于多靶点,从抗炎、抗凋亡等多种途径发挥治疗IS的作用。
Mechanism of Qingre Huatan Tongfu formula in treating ischemic stroke based on network pharmacology
Objective:To explore the potential mechanism of Qingre Huatan Tongfu formula(HTF)in the treat-ment of ischemic stroke(IS)based on network pharmacology and animal experiments.Methods:The active in-gredients of HTF were screened using TCMSP and BATMAN databases and the potential targets of these active ingredients were predicted.Disease-related targets were screened in GeneCards,OMIM,TTD,and Drugbank da-tabases.The protein interaction relationship was obtained using the String database.Key targets underwent GO and KEGG enrichment analysis using Metascape.The animal model was constructed for experimental verifica-tion.Neural function scores,2,3,5-triphenyltetrazolium chloride(TTC)staining,hematoxylin-eosin(HE)stain-ing,Nissl staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and immuno-histochemistry were used to verify the network pharmacological enrichment results.Results:By conducting net-work pharmacological analysis,the main active ingredients were predicted to include apigenin,quercetin,kaemp-ferol,and β-sitosterol.These ingredients acted on potential targets such as serine/threonine kinase 1(AKT1),in-terleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transformation-associated protein 53(TP53)and other poten-tial targets.The key pathways involved included lipid and atherosclerosis,MAPK signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,IL-17 signaling pathway,and hypoxia-inducible factor-1(HIF-1)sig-naling pathway,etc.The experimental results showed that HTF could significantly reduce the nerve function score and the volume of cerebral infarction in cerebral ischemia-reperfusion rats(P<0.05),improve the survival of neurons(P<0.05),and significantly reduce the cell apoptosis(P<0.05).Conclusion:Based on network phar-macology and animal experiments,it is found that HTF can play a role in the treatment of IS through multiple components acting on multiple targets,involving various pathways such as anti-inflammation and anti-apoptosis.

network pharmacologyQingre Huatan Tongfu formulaischemic stroke

尹建新、武鹏、张泆琳、张佳佳、谢爱泽

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广西医科大学第一附属医院,南宁 530021

广西医科大学附属肿瘤医院,南宁 530021

网络药理学 清热化痰通腑方 缺血性脑卒中

广西医疗卫生适宜技术开发与推广应用项目广西中医药重点学科建设项目国家中医药管理局全国名老中医药专家传承工作室建设资助项目

S2018050GZXK-Z-20-52国中医药人教发[2014]20号

2024

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子:0.788
ISSN:1005-930X
年,卷(期):2024.41(1)
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