基于网络药理学探讨“运脾法”治疗儿童腺样体肥大的机制及实验验证  

Mechanism and experimental verification of“Activating Spleen Treatment”in treating adenoidal hypertrophy of children based on network pharmacology

作　　者：张奕星 林燕[2] 杨铭[3] 姜之炎[2] ZHANG Yi-xing;LIN Yan;YANG Ming;JIANG Zhi-yan(Dept of Paediatrics,Lishui Hospital of Traditional Chinese Medicine,Lishui Zhejiang 323000,China;Dept of Paediatrics,Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China;GCP Center,Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)

机构地区：[1]丽水市中医院儿科,浙江丽水323000 [2]上海中医药大学附属龙华医院儿科,上海200030 [3]上海中医药大学附属龙华医院GCP中心,上海200030

出　　处：《中国药理学通报》2023年第12期2361-2369,共9页Chinese Pharmacological Bulletin

基　　金：国家自然基金资助项目(No 82174433);中医儿科专项建设项目(No LH02.09.018);上海市进一步加快中医药传承创新发展三年行动计划项目[No ZY(2021-2023)-0206-01];上海市非物质文化遗产项目(徐氏儿科)(No LH02.049)。

摘　　要：目的基于网络药理学方法探讨运脾药对“苍术-薏苡仁”治疗儿童腺样体肥大(adenoidal hypertrophy,AH)的药理机制。方法筛选“苍术-薏苡仁”的活性成分及相关靶点,构建“药物-成分-靶点”可视化网络图;检索儿童AH疾病相关靶点,构建“药物-疾病”交集靶点PPI网络;对核心靶点进行富集分析,并构建“靶点-通路”网络;Western blot法检测不同组别小鼠脾组织中目标靶点蛋白表达,验证苍术酮通过HIF-1α-sumoylation调节炎症因子的表达。结果得到“苍术-薏苡仁”药物靶点71个,儿童AH疾病相关靶点337个,“药物-疾病”交集靶点30个;“苍术-薏苡仁”主要活性成分为豆甾醇、苍术酮等,其参与的生物学过程有管形态形成、对激素的反应等,涉及的细胞成分有膜筏、转录调节因子复合物等,相关靶点功能主要富集于转录因子结合、蛋白质结构域特异性结合等,其涉及的主要信号通路有HIF-1信号通路、VEGF信号通路等;动物实验结果显示苍术酮治疗组SUMO-1、HIF-1α、VEGF及VEGF-R蛋白表达量均较模型组下调(P<0.05)。结论“运脾法”治疗儿童AH是通过多成分、多靶点、多通路实现的,主要从抗炎、免疫调节、抗氧化等方面发挥其治疗儿童AH的作用。Aim To investigate the pharmacological mechanism of the couplet medicines“Cangzhu-Yiyiren”in treating adenoid hypertrophy(AH)of children based on network pharmacology.Methods To screen the active ingredient and relevant targets of the couplet medicines“Cangzhu-Yiyiren”,a visual network map of“Drug-Component-Target”was constructed;related targets of AH were retrieved and standardized,and A PPI network to treat AH of children by“Cangzhu-Yiyiren”was constructed.Enrichment analysis was performed for the core targets,and a“targets-pathways”network was constructed.The expression of target pro-teins from spleen tissues of different groups was determined by Western blot to verify that atractylone regulated the expression of inflammatory factors by HIF-1α-SUMOylation.Results A total of 71 drug-related targets and 337 disease-related targets for AH in children were obtained,and there were 30“Drug-Disease”intersection targets.The main active components of the couplet medicines“Cangzhu-Yiyiren”were stigmasterol,atractylone and so on.The biological processes mainly involved in were tube morphogenesis,response to hormone,the main cellular components involved in were membrane raft,transcription regulator complex,and the molecular function of related targets were mainly enriched in the transcription factor binding,protein domain specific binding,etc.The enrichment analysis indicated that it was associated with apoptosis-multiple species,VEGF signaling pathway,and HIF-1 signaling pathway,etc.The results of animal experiments showed that SUMO-1,HIF-1α,VEGF and VEGF-R protein expression were all down-regulated compared with the model group(P<0.05).Conclusions The treatment of pediatric AH which takes the“Activating Spleen Treatment of Nasa”as the guiding ideology,is realized through multi-components,multi-target,multi-pathways,and mainly from the anti-inflammatory,immune regulation,antioxidant and other aspects to play its role in the treatment of children with AH.

关 键 词：运脾治鼻 网络药理学 腺样体肥大 机制研究 苍术酮 氧化应激 

分 类 号：R-332[医药卫生] R223.1R282.71R319R349.1R765