中药药理与临床2025，Vol.41Issue(5)：33-38,6.
黄芪多糖调节TLR4/NLRP3/Caspase-1信号通路对糖尿病认知障碍大鼠的保护作用及机制研究
Astragalus Polysaccharide Protects Rats from Diabetes with Cognitive Impairment by Regulating TLR4/NLRP3/Caspase-1 Signaling Pathway
摘要
Abstract
Objective:To explore the protective effect of Astragalus polysaccharide on diabetes with cognitive impairment in rats and its possible mechanism.Methods:The rat model of diabetes with cognitive impairment was established by feeding a high-fat diet and intraperitoneal in-jection of streptozotocin(STZ).The successfully modeled rats were randomized into a model control group,Astragalus polysaccharide(100,200,and 400 mg/kg)groups,and an inhibitor(TAK-242,3 mg/kg)group,with 12 rats in each group.Another 12 rats were regarded as the normal control group.After administration,the random blood glucose level in tail vein blood was measured by a blood glucose meter.Morris water maze test was conducted to evaluate the spatial learning and memory ability of rats.The enzyme-linked immunosorbent assay(ELISA)was employed to measure the serum levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and monocyte chemoattractant protein-1(MCP-1).The thiobarbituric acid(TBA)method was employed to determine the serum level of malondialdehyde(MDA),and the water-sol-uble tetrazolium-1(WST-1)method was employed to measure the activity of superoxide dismutase(SOD)in the serum.Terminal-deoxynu-cleoitidyl transferase-mediated nick end labeling(TUNEL)was employed to detect neuron apoptosis in rat hippocampus.Western blotting was employed to determine the protein levels of factors in the Toll-like receptor 4(TLR4)/Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)signaling pathway in rat hippocampus.Results:Compared with the normal control group,the model control group showed elevations in the random blood glucose level and serum levels of IL-6,TNF-α,MCP-1,and MDA,an increase in the apoptosis rate of neurons in the hippocampus,and up-regulation in the expression of TLR4,phospho-nuclear factor-κB(p-NF-κB)/NF-κB,NLRP3,Caspase-1,IL-1β,and IL-18.Furthermore,the modeling prolonged the escape latency,reduced platform crossings,decreased the percentage of residence time in the target quadrant,and weakened the activity of SOD in the serum(P<0.05).Compared with the model con-trol group,Astragalus polysaccharide(100,200,and 400 mg/kg)and TAK-242 lowered the serum levels of IL-6,TNF-α,MCP-1,and MDA,decreased the apoptosis rate of neurons in the hippocampus,down-regulated the protein levels of TLR4,p-NF-κB/NF-κB,NLRP3,Caspase-1,IL-1β,and IL-18,shortened the escape latency,and increased the platform crossings,the percentage of residence time in the target quadrant,and SOD activity in the serum(P<0.05).Moreover,Astragalus polysaccharide exerted the effects in a dose-dependent manner.Conclusion:Astragalus polysaccharide may play a neuroprotective role in the rat model of diabetes with cognitive impairment by inhibiting the activation of the TLR4/NLRP3/Caspase-1 signaling pathway.关键词
黄芪多糖/糖尿病认知障碍/Toll样受体4/Nod样受体蛋白3/半胱天冬酶信号通路Key words
Astragalus polysaccharide/Diabetes with cognitive impairment/Toll-like receptor 4/Nod-like receptor protein 3/cysteinyl aspar-tate-specific proteinase-1(Caspase-1)signaling pathway引用本文复制引用
李希,武洁,王英虎,赵层闪,唐艳阁,康宁琳,田军彪..黄芪多糖调节TLR4/NLRP3/Caspase-1信号通路对糖尿病认知障碍大鼠的保护作用及机制研究[J].中药药理与临床,2025,41(5):33-38,6.基金项目
河北省中医药管理局科研计划项目(编号:2021041). （编号:2021041）
