首页|基于网络药理学探讨相关中药作用于自闭症关键基因的分子机制

基于网络药理学探讨相关中药作用于自闭症关键基因的分子机制

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目的 基于网络药理学对自闭症关键基因进行初步筛选,探讨与自闭症的潜在靶点、生物学过程和信号通路相关的中药。方法 以从GEO数据库选取GSE29691数据集作为研究样本,基于GEO2R筛选差异基因,利用微生信网络工具对差异基因进行GO和KEGG分析,利用Cytoscape软件筛选关键靶点并构建模块,将关键靶点导入Coremine医学数据库进行可视化分析,筛选潜力中药。结果 对来自GSE29691的原始数据集进行处理,筛选出164个与自闭症患儿显著不同的基因。GO和KEGG分析表明,差异基因主要参与调控EPK1和EPK2蛋白连接、正向调节T细胞活化和白细胞介导的细胞毒性等生物学过程,并与沙门氏菌感染途径、糖尿病心肌病相关。PPI网络图表明,调控粒溶蛋白(GNLY)、T细胞调节趋化因子(CCL5),溶酶体关联膜蛋白1(LAMP1)、自然杀伤细胞颗粒蛋白7(NKG7)、T细胞表面单程膜糖蛋白(CD3E)、半胱氨酸蛋白酶抑制剂(CST7)、穿孔素1重组蛋白(PRF1)、组织蛋白酶(CTSW)、成纤维细胞成长因子结合蛋白(FGFBP2)等可作为治疗自闭症的潜在靶点。冬虫夏草、蚕沙、蚕蛾与多个自闭症关键基因相关,蚕沙、蚕蛾均与CCL5、钙连蛋白(CANX)、LAMP1等多个关键基因相关联;冬虫夏草与GNLY、CCL5、LAMP1等多个关键基因相互映射;另外冬虫夏草、蚕沙等活性成分通过肿瘤坏死因子(TNF)、Toll样受体4(TLR4)间接参与GNLY、CCL5、LAMP1、CANX等自闭症关键基因,这可能成为治疗自闭症的潜在目标中药。结论 冬虫夏草、蚕蛾、蚕沙中的活性化合物可通过作用于CCL5、LAMP1、CANX等多个靶点调节炎症和免疫系统,对自闭症起到治疗作用。
Exploring the molecular mechanism of related Chinese medicines acting on key genes in autism based on network pharmacology
Objective To screen the key genes of autism based on network pharmacology,and explore the po-tential targets,biological processes and signaling pathways related to traditional Chinese medicines in autism.Meth-ods GSE29691 dataset was selected from GEO database as research sample.The differential genes were screened based on GEO2R,the differential genes were analyzed by GO and KEGG using Wei Sheng Xin network tool,key tar-gets were screened and modules were built using Cytoscape software,key targets were imported into Coremine medi-cal database for visual analysis,and potential Chinese medicines were screened.Results The original dataset from GSE29691 was processed to screen out 164 genes that were significantly different from those in autistic patients.GO and KEGG analysis showed that differential genes were mainly involved in the regulation of EPK1 and EPK2 protein linkage,positive regulation of T cell activation and leukocyte mediated cytotoxicity,and were associated with salmo-nella infection pathways and diabetic cardiomyopathy.The PPI network map showed that the regulatory granolysin(GNLY),T cell regulatory chemokine(CCL5),Lysosome associated membrane protein 1(LAMP1),natural killer cell granuloprotein 7(NKG7),T cell surface single pass membrane glycoprotein(CD3E),cysteine protease inhibi-tor(CST7),perforin 1 recombinant protein(PRF1),histoprotease(CTSW),fibroblast growth factor binding pro-tein(FGFBP2),etc as a potential target for treating autism.Cordycepssinensis,silkworm sand and silkworm moth are related to several key genes of autism,and silkworm sand and silkworm moth are related to CCL5,CANX,LAMP1 and other key genes.Cordyceps sinensis and GNLY,CCL5,LAMP1 and other key genes map each other;In addition,active ingredients such as Cordycepssinensis and silkworm sand indirectly participate in key autism genes such as GNLY,CCL5,lysosomal associated membrane protein 1(LAMP1)and calponectin(CANX)through TNF and TLR4,which may become potential target Chinese medicine for the treatment of autism.Conclusion The active compounds in Cordycepssinensis,silkworm moth and silkworm sand can regulate inflammation and immune system by acting on multiple targets such as CCL5,LAMP1 and CANX,and play a therapeutic role in autism.

autismcordycepssinensissilkworm sandsilkworm mothgene targetsignal pathmolecular mech-anismnetwork pharmacology

孙文玉、毕鸿雁

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山东中医药大学附属医院康复医学科,山东 济南 250014

自闭症 冬虫夏草 蚕沙 蚕蛾 基因靶点 信号通路 分子机制 网络药理学

2024

中医儿科杂志
甘肃中医学院,中华中医药学会

中医儿科杂志

影响因子:0.82
ISSN:1673-4297
年,卷(期):2024.20(5)