中国药理学通报2026，Vol.42Issue(10)：1847-1856,10.DOI:10.12360/CPB202601012
有氧运动联合山姜素协同调节SphK1/S1P/S1PR2信号通路对脂多糖诱导抑郁小鼠神经炎症的改善作用及机制
Synergistic regulation of SphK1/S1P/S1PR2 signaling pathway by aerobic exercise and alpinetin in alleviating neuroinflammation in lipopolysaccharide-induced depressive mice
摘要
Abstract
Aim To investigate the synergistic effects of aerobic exercise combined with alpinetin on neuroin-flammation in lipopolysaccharide(LPS)-induced de-pressive mice by modulating the SphK1/S1P/S1PR2 signaling pathway.Methods Seventy male 8-week-old C57BL/6J mice were randomly divided into seven groups(n=10):control group,model group,aerobic exercise group,low-dose alpinetin group,high-dose alpinetin group,aerobic exercise+high-dose alpinetin group,and positive control group.The intervention pe-riod lasted 28 days.Behavioral tests included forced swim,tail suspension,and sucrose preference tests.Hippocampal tissues were collected to measure IL-6 and TNF-α levels,along with protein expression of Iba-1,iNOS,CD86,Arg-1,CD206,SphK1,S1P,and S1PR2.In vitro,BV-2 cells were assigned to the same seven groups(n=6).A pathway validation experiment(n=6)involved treating BV-2 cells with the SphK1 ac-tivator K6PC-5.Cell viability,supernatant IL-6/TNF-α levels,and pathway-related protein expression were analyzed.Results In vivo results showed that the model group exhibited prolonged immobility time in forced swim and tail suspension tests,reduced sucrose preference,and elevated hippocampal IL-6 and TNF-α levels.All intervention groups significantly improved these indices.The interventions reduced Iba-1,i NOS,CD86,SphK1,S1P,and S1PR2 expression while upregulating Arg-1 and CD206 in BV-2 cells.In vitro findings mirrored the in vivo trends,with the com-bined intervention showing superior effects compared to single interventions in certain parameters.The SphK1 activator K6PC-5 partially reversed these ef-fects.Conclusions Aerobic exercise combined with alpinetin synergistically regulates the SphK1/S1P/S1PR2 signaling pathway,inhibits M1-type microglial activation,alleviates neuroinflammation,and im-proves depressive-like behaviors.关键词
有氧运动/山姜素/抑郁症/神经炎症/鞘氨醇激酶1/鞘氨醇-1-磷酸Key words
aerobic exercise/alpinetin/depression/neuroinflammation/sphingosine Kinase 1/sphingo-sine-1-phosphate分类
医药卫生引用本文复制引用
万华喆,周灿,梁婷,夏诗雨,黄敏霞,肖京洋..有氧运动联合山姜素协同调节SphK1/S1P/S1PR2信号通路对脂多糖诱导抑郁小鼠神经炎症的改善作用及机制[J].中国药理学通报,2026,42(10):1847-1856,10.基金项目
江西省自然科学基金项目(No 20232BAB205012) （No 20232BAB205012）
