摘要
目的 基于体内实验、代谢组学及网络药理学探讨降浊合剂治疗2型糖尿病(type 2 diabetes mellitus,T2DM)的药效物质基础及作用机制。方法 构建高脂饮食联合链脲佐菌素诱导的T2DM小鼠模型,给予二甲双胍和不同剂量降浊合剂干预8周。通过血清生化分析、肾组织病理染色(HE/PAS)及ELISA检测评估药效,代谢组学检测肝脏代谢变化。采用QTOF-LC-MS技术结合TCMSP数据库筛选降浊合剂化学成分,在TCMSP和SwissTargetPrediction数据库预测药物作用靶点,在GeneCards、OMIM等数据库预测T2DM相关靶点,获得共同靶点后运用网络药理学构建“药物-成分-靶点”网络,通过STRING、Metascape进行PPI网络和通路富集分析,结合AutoDock vina进行分子对接验证。结果 降浊合剂显著改善T2DM小鼠糖脂代谢及肾脏损伤,代谢组学显示其可逆转肝脏代谢紊乱。网络药理学筛选出260个共同靶点,涉及AGE-RAGE等关键信号通路。分子对接证实关键成分(大豆苷元、葛根素等)与核心靶点(IL-6、TNF-α等)结合良好,动物实验验证其通过抑制AGE-RAGE信号轴调控炎症因子释放。结论 降浊合剂可降低T2DM小鼠的血糖水平,改善胰岛素抵抗情况,机制涉及改善肝脏代谢紊乱、抑制炎症反应,该研究结果为降浊合剂的临床应用提供理论参考。
OBJECTIVE To investigated the material basis and underlying mechanism of Jiangzhuo decoction(JZD)in the treatment of type 2 diabetes mellitus(T2DM)by in vivo experiments,metabolomics and network pharmacology.METHODS A T2DM mouse model was constructed using a high-fat diet combined with streptozotocin.Mice were treated with metformin or low/medium/high doses of JZD for 8 weeks.Serum biochemical parameters,renal histopathology(HE and PAS staining),and renal protein expression(ELISA)were analyzed.Liver metabolomic profiles were assessed.Components of JZD were screened via QTOF-LC-MS and the TCMSP database.Potential targets of JZD and T2DM-related genes were predicted via SwissTargetPrediction,GeneCards,and OMIM databases.Common targets were used to construct a"herb-compound-target"network.STRING and Metascape were employed for protein-protein interaction(PPI)network and pathway enrichment analysis.Molecular docking validation was performed using AutoDock Vina.RESULTS JZD significantly improved glucose-lipid metabolism and alleviated renal injury in T2DM mice by reversing hepatic metabolic disturbances,as demonstrated through metabolomics analysis.Network pharmacology identified 260 common targets,with AGE-RAGE signaling as a key enriched pathway.Molecular docking confirmed strong binding between core components(daidzein,puerarin,etc.)and critical targets(IL-6,TNF-α,etc.).Animal experiments validated JZD’s inhibition of the AGE-RAGE axis and downstream inflammatory cytokine release.CONCLUSION JZD ameliorates hyperglycemia and insulin resistance in T2DM mice via regulating hepatic metabolic homeostasis and inhibiting inflammation,providing a mechanistic basis for its clinical translation.
作者
骆震
高玉丽
周开
李婉姝
方晴
金鑫
林杭娟
LUO Zhen;GAO Yuli;ZHOU Kai;LI Wanshu;FANG Qing;JIN Xin;LIN Hangjuan(Ningbo Municipal Hospital of TCM,Affiliated Hospital of Zhejiang Chinese Medical University,Department of TCM Internal Medicine,Ningbo 315016,China;Ningbo Municipal Hospital of TCM,Affiliated Hospital of Zhejiang Chinese Medical University,Department of Pharmacy,Ningbo 315016,China)
出处
《中国现代应用药学》
北大核心
2025年第12期2035-2046,共12页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省中医药科技计划(2022ZB321)
宁波市重点研发计划(2022Z135)
宁波市医学重点学科建设项目(2022-ZF02)
宁波市中药制剂中心建设项目(zyy23011)。
