重楼皂苷Ⅰ治疗病毒性心肌炎的作用机制  

Mechanism of PolyphyllinⅠAgainst Viral Myocarditis

作　　者：彭纪铭 陈娜娜 伏瑶 Peng Jiming;Chen Nana;Fu Yao(Key Laboratory of Neurophysiology,Health Commission of Shandong Province,Linyi 276000,China;Pharmaceutical Department,Linyi People's Hospital,Linyi 276000,China;School of Basic Medicine,Shandong University,Jinan 250100,China;Central Laboratory,Linyi People's Hospital,Linyi 276000,China)

机构地区：[1]山东省卫生健康委员会医药卫生神经生理学重点实验室,山东临沂276000 [2]临沂市人民医院药学部,山东临沂276000 [3]山东大学基础医学院,山东济南250100 [4]临沂市人民医院中心实验室,山东临沂276000

出　　处：《南开大学学报(自然科学版)》2025年第1期85-91,共7页Journal of Nankai University(Natural Sience)

基　　金：国家自然科学基金青年基金(32200629);山东省自然科学基金青年基金(ZR2022QH168);江苏省新药研究与临床药学重点实验室开放资助项目(XZSYSKF2021033);临沂市人民医院博士科研创新基金(2021LYBS01)。

摘　　要：为探讨重楼皂苷Ⅰ(PPⅠ)对病毒性心肌炎(VMC)模型大鼠的治疗作用及机制,采用网络药理学方法预测PPⅠ治疗VMC的潜在作用靶点,将重楼皂苷Ⅰ与疾病靶点进行Venny分析,交集靶点构建蛋白质-蛋白质相互作用网络;David数据库对交集靶点基因进行基因本体富集分析(GO)和京都基因与基因组百科全书富集分析(KEGG);采用Autodock软件对关键潜在靶标进行分子对接,以验证网络分析结果的可靠性.同时,建立VMC模型探讨PPⅠ对VMC的治疗作用.网络药理学分析发现,PPⅠ对VMC共有51个潜在治疗靶点,其中Degree值排名靠前的有IL-6、JUN、STAT3等靶点,主要涉及NF-κB信号通路、PI3K/Akt信号通路、MAPK信号通路等;分子对接结果显示结合能小于-29.4 kJ/mol,表明PPⅠ对治疗VMC潜在靶标有较强的亲和能力.动物实验结果显示,PPI能够明显改善模型大鼠心肌组织病理损伤,降低其血清中炎症因子含量;RT-PCR及western blot结果显示,PPI能显著降低VMC模型大鼠心肌组织Cvb3 mRNA表达水平,可显著下调VMC模型大鼠心肌组织TLR4/MyD88/NF-κB及P38 MAPK信号通路蛋白表达.本研究结果表明,PPⅠ可能通过下调TLR4/MyD88/NF-κB及P38 MAPK信号通路相关蛋白的表达,降低血清炎症因子含量,改善心肌损伤,起到对VMC模型大鼠的治疗作用.To explore the therapeutic effect and mechanism of PolyphyllinⅠ(PPⅠ)on viral myocarditis(VMC)model mice through network pharmacology,molecular docking technology and animal experiments.The potential targets of PPⅠ in the treatment of VMC were predicted by network pharmacology,and the PPⅠ and the disease targets were analyzed by Venn,and the protein mutual aid network was constructed by crossing the targets.David database carried out GO enrichment analysis and KEGG enrichment analysis on intersection target genes;Autodock software was used to dock the key potential targets to verify the reliability of the network analysis results.At the same time,the VMC model was established to explore the therapeutic effect of PPⅠ on VMC.According to the analysis of network pharmacology,PPI had 51 potential therapeutic targets for VMC,among which IL-6,JUN,STAT3 and other targets rank high in Degree value,mainly involving NF-κB signaling pathway,PI3K/Akt signaling pathway,MAPK signaling pathway,etc.Molecular docking showed that the binding energy was less than-29.4 kJ/mol,which indicated that PPI had strong affinity for treating potential targets of VMC,and the network analysis results are reliable.Animal experiments showed that PPⅠ can obviously improve the pathological injury of myocardial tissue in model rats and reduce the content of inflammatory factors in their serum.RT-PCR experiment showed that PPⅠ could significantly reduce the expression level of Cvb3 mRNA in myocardial tissue of VMC model rats.Western blot experiment showed that PPⅠcould significantly down-regulate the expression of TLR4/MyD88/NF-κB and P38 MAPK signaling pathway proteins in myocardial tissue of VMC model rats.The potential target of PPI may play a therapeutic role in VMC model rats by down-regulating the expression of TLR4/MyD88/NF-κB and P38 MAPK signaling pathway-related proteins,reducing the content of serum inflammatory factors and improving myocardial injury.

关 键 词：重楼皂苷Ⅰ 病毒性心肌炎 网络药理学 分子对接 炎症因子 

分 类 号：R932[医药卫生—生药学]