机构地区:[1]广州中医药大学,广东广州510006 [2]广东祈福医院,广东广州511400
出 处:《广州中医药大学学报》2023年第10期2597-2605,共9页Journal of Guangzhou University of Traditional Chinese Medicine
摘 要:【目的】综合生物信息学、网络药理学和分子对接探讨补肾健脾方(由淫羊藿、鹿角胶、黄芪、山药等组成)改善2型糖尿病(T2DM)的作用机制,并通过动物实验验证。【方法】通过Mfuzz分析正常样本由糖耐量异常转变为T2DM的模块基因,并通过差异分析进一步筛选T2DM的疾病靶点;通过TCMSP、BATMAN数据库筛选补肾健脾方的活性成分及其作用靶点,随后获取补肾健脾方治疗T2DM的靶点并分析生物功能。比较补肾健脾方治疗组db/db小鼠胰岛功能、氧化应激指标、胰腺细胞凋亡与对照组的差异。【结果】共筛选出77个补肾健脾方的作用靶点,通过富集分析,77个靶点与氧化应激过程关系密切,并进一步筛选出2个核心靶点FOS、NOTCH1,通过分子对接证明了补肾健脾方主要活性成分与核心靶点结合稳定。最后,通过动物实验证明,与对照组比较,治疗组db/db小鼠稳态模型评估的胰岛素抵抗指数(HOMA-IR)升高,氧化应激指标丙二醛(MDA)降低、超氧化物歧化酶(SOD)活性升高,胰腺组织FOS、NOTCH1表达量降低,胰腺组织凋亡蛋白Bax和Caspase-3表达量降低、凋亡抑制蛋白Bcl-2表达量升高(P<0.05或P<0.01)。【结论】补肾健脾方可通过减轻氧化应激,降低胰岛细胞凋亡,从而改善胰岛素抵抗以延缓T2DM的进展。Objective To investigate the mechanism of Bushen Jianpi Prescription(composed of Epimedii Folium,Cervi Cornus Colla,Astragali Radix,Dioscoreae Rhizoma,etc.)in improving T2DM based on bioinformatics,network pharmacology and molecular docking,and validated by animal experiments.Methods The modular genes of normal samples transformed from abnormal glucose tolerance to T2DM were analyzed by Mfuzz,and the disease targets of T2DM were further screened by differential analysis;the active components of Bushen Jianpi Prescription and their action targets were screened by TCMSP and BATMAN databases,and the targets of Bushen Jianpi Prescription for the treatment of T2DM were subsequently obtained and the biological functions were analyzed.Then,the differences in islet function,oxidative stress index and pancreatic cell apoptosis in db/db mice between Bushen Jianpi Prescription treatment group and control group were compared.Results In this study,77 action targets of Bushen Jianpi Prescription were screened.Through enrichment analysis,77 targets were closely related to oxidative stress processes,and 2 core targets,FOS and NOTCH1,were further screened,and the binding of the main active components of Bushen Jianpi Prescription to the core targets was demonstrated to be stable through molecular docking.Finally,animal experiments demonstrated that compared with the control group,the homeostasis model assessment of insulin resistance(HOMA-IR)of db/db mice in the treatment group was increased,the index of oxidative stress malondialdehyde(MDA)was decreased,the activity of superoxide dismutase(SOD)was increased,and the expressions of FOS and NOTCH1 in pancreas were decreased.The expressions of apoptosis protein Bax and Caspase-3 were decreased and the expression of apoptosis inhibitor protein Bcl-2 was increased in pancreatic tissue(P<0.05 or P<0.01).Conclusion By alleviating oxidative stress,reducing islet cell apoptosis and thereby improving insulin resistance,Bushen Jianpi Prescription can slow down the progression of T2DM.
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