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OA
Synergistic regulation of SphK1/S1P/S1PR2 signaling pathway by aerobic exercise and alpinetin in alleviating neuroinflammation in lipopolysaccharide-induced depressive mice
目的 探讨有氧运动联合山姜素调控鞘氨醇激酶1(sphingosine kinase 1,SphK1)/鞘氨醇-1-磷酸(sphingosine-1-phosphate,S1P)/S1P受体2(S1P receptor 2,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.方法 70只8周龄C57BL/6J雄鼠随机分为7组(n=10):对照组、模型组、有氧运动组、低/高剂量山姜素组、有氧运动+高剂量山姜素组、阳性对照组.试验期28 d.进行强迫游泳、悬尾和蔗糖偏好测试.取小鼠海马组织,检测IL-6和TNF-α水平,钙结合蛋白-1(ionized calcium-binding adapter mol-ecule-1,Iba-1)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、分化簇 86(cluster of differentiation 86,CD86)、精氨酸酶-1(arginase-1,Arg-1)、CD206、SphK1、S1P、S1PR2蛋白表达.BV-2细胞参考体内试验分为同样的7组(n=6).另设通路验证试验(n=6),使用 SPHK1 激活剂K6PC-5处理BV-2细胞.检测细胞活力,培养上清液IL-6和TNF-α水平,通路相关蛋白表达.结果 体内实验结果显示,模型组小鼠强迫游泳和悬尾不动时间明显延长,蔗糖偏好率降低,海马组织IL-6、TNF-α水平升高,各干预组均明显改善以上指标.各干预组明显降低BV-2细胞Iba-1、iNOS、CD86、SphK1、S1P、S1PR2表达,上调Arg-1、CD206表达.体外试验结果和体内试验趋势相似,联合干预组在部分指标中的效果优于单独干预组.SPHK1激活剂K6PC-5处理后,干预效果被部分抵消.结论 有氧运动联合山姜素能协同调控SphK1/S1P/S1PR2信号通路,抑制小胶质细胞M1型活化,减轻神经炎症,改善抑郁样行为.
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.
万华喆;周灿;梁婷;夏诗雨;黄敏霞;肖京洋
南昌航空大学科技学院,江西 南昌 330000南昌航空大学科技学院,江西 南昌 330000南昌航空大学科技学院,江西 南昌 330000南昌航空大学科技学院,江西 南昌 330000南昌航空大学科技学院,江西 南昌 330000南昌大学第二附属医院,江西 南昌 330036
医药卫生
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
aerobic exercisealpinetindepressionneuroinflammationsphingosine Kinase 1sphingo-sine-1-phosphate
《中国药理学通报》 2026 (10)
1847-1856,10
江西省自然科学基金项目(No 20232BAB205012)
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