姜黄素改善糖尿病小鼠脑部Aβ沉积机制研究  

Curcumin Improved Aβ Deposition in the Brain of Diabetic Mice Through PI3K/AKT/GSK-3β Pathway

作　　者：张雨晴 何昂 郭霜[2] 雷敏 刘秀芬[2] 郭西英 ZHANG Yu-qing;HE Ang;GUO Xi-ying(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,湖北咸宁437100 [2]湖北科技学院糖尿病心脑血管病变湖北省重点实验室

出　　处：《湖北科技学院学报（医学版）》2024年第4期282-286,共5页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：湖北省科技计划项目(2021DFE025);湖北省教育厅项目(BXLBX0808)。

摘　　要：目的 结合网络药理学、分子对接及实验验证姜黄素(Cur)缓解糖尿病小鼠脑部β-淀粉样蛋白(Aβ)沉积的分子机制。方法 应用网络药理学筛选Cur与糖尿病小鼠认知功能障碍(DCD)的共同靶点;Autodock软件进行分子对接;Western blot、q-PCR检测相关蛋白及mRNA表达水平。结果 Cur与DCD的共同靶点主要富集于PI3K/AKT信号通路;分子对接显示Cur与AKT1、NF-κB和TNF-α结合;Western blot显示,DM小鼠p-PI3K、p-AKT、p-GSK-3β、BACE1蛋白表达减少,APP蛋白表达增加,Cur给药逆转了相关蛋白的表达;DM小鼠TNF-α、IL-6、IL-1β炎性因子的mRNA水平显著增加,Cur给药逆转了相关基因的表达。结论 Cur可能通过PI3K/AKT/GSK-3β通路抑制炎症改善糖尿病小鼠脑部Aβ的沉积。Objective To investigate the molecular mechanism by curcumin(Cur) alleviates Aβ deposition in the brain of diabetic mice through network pharmacology,molecular docking and experiments.Methods Network pharmacology was used to screen the common targets of Cur and cognitive dysfunction in diabetic mice(DCD).Autodock was used for molecular docking.Western blot and qPCR were used to detect the expression levels of related proteins and mRNA.Results The majority of the common targets between Cur and DCD were found to be enriched in the PI3K/AKT signaling pathway.Molecular docking revealed that Cur bound to AKT1,NF-κB,and TNF-α.Western blot demonstrated that DM mice had increased expression of APP proteins and decreased expression of p-PI3K,p-AKT,p-GSK-3β and BACE1 proteins,which could be reversed by the administration of Cur.DM mice had significantly increased levels of TNF-α,IL-6,and IL-1β inflammatory factors,and the expression of these genes could be reversed by the administration of Cur.Conclusion Cur may improve the deposition of Aβ in the brain of diabetic mice through PI3K/AKT/GSK-3β pathway.

关 键 词：网络药理学 糖尿病 姜黄素 AΒ 

分 类 号：R965.2[医药卫生—药理学]