基于cAMP/PKA信号通路探讨连翘苷对多发性抽动症神经炎症的影响OA
An Exploration of the Effect of Phillyrin on Neuroinflammation in Tourette Syndrome via the cAMP/PKA Signaling Pathway
目的:研究连翘苷对多发性抽动症(TS)大鼠的作用及机制.方法:建立TS大鼠模型,随机分为模型组、连翘苷(50mg/kg)组和连翘苷(50mg/kg)+蛋白激酶A(PKA)抑制剂H-89(2mg/kg)组,另取正常大鼠作为对照组,每组12只.各组灌胃或腹腔注射相应药物,每天1次,持续4周.采用行为学指标评价大鼠行为;ELISA法检测血清5-羟色胺(5-HT)、多巴胺(DA)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)及纹状体5-HT、DA、环磷酸腺苷(cAMP)水平;HE和DHE染色分别观察纹状体病理及活性氧(ROS)水平变化;免疫组化染色检测纹状体TNF-α、IL-1β阳性表达;Western blot检测纹状体PKA、cAMP反应元件结合蛋白(CREB)表达及其磷酸化水平.结果:与对照组比较,模型组大鼠运动行为学和刻板行为学评分升高(P＜0.05);纹状体神经元坏死、排列紊乱及炎性细胞浸润明显;血清5-HT 降低,DA、TNF-α、IL-1β 水平升高(P＜0.05);纹状体 5-HT、DA、cAMP、p-PKA/PKA、p-CREB/CREB蛋白水平降低,TNF-α、IL-1β、ROS水平升高(P＜0.05).与模型组比较,连翘苷组大鼠运动行为学和刻板行为学评分降低(P＜0.05);纹状体神经元病理改善;血清5-HT升高,DA、TNF-α、IL-1β水平降低(P＜0.05);纹状体 5-HT、DA、cAMP、p-PKA/PKA、p-CREB/CREB 蛋白水平升高,TNF-α、IL-1β、ROS水平降低(P＜0.05).H-89可逆转连翘苷对TS大鼠的改善作用(P＜0.05).结论:连翘苷能够改善TS大鼠行为学和神经炎症,其机制可能与调控cAMP/PKA信号通路相关.
Objective:To investigate the effects and mechanisms of phillyrin on rats with Tourette Syn-drome(TS).Methods:A rat model of TS was established and randomly divided into a model group,a phill-yrin(50mg/kg)group,and a phillyrin(50mg/kg)+protein kinase A(PKA)inhibitor H-89(2mg/kg)group.Additionally,normal rats were selected as a control group.Each group contained 12 rats which re-ceived the corresponding drugs via gavage or intraperitoneal injection once daily for 4 weeks.Behavioral indi-cators were used to evaluate rat behavior.ELISA was used to detect serum levels of 5-hydroxytryptamine(5-HT),dopamine(DA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and striatal levels of 5-HT,DA,and cyclic adenosine monophosphate(cAMP).Hematoxylin-eosin(H&E)and dihydroethidium(DHE)staining were used to observe striatal pathology and changes in reactive oxygen species(ROS)levels,respectively.Immunohistochemical staining was used to detect the positive expression of TNF-α and IL-1β in the striatum.Western blot was used to detect the expression and phosphorylation levels of PKA and cAMP re-sponse element-binding protein(CREB)in the striatum.Results:Compared with the control group,rats in the model group exhibited elevated scores for motor behaviour and stereotyped behaviour(P＜0.05);marked neuronal necrosis,disorganised arrangement,and inflammatory cell infiltration were observed in the striatum;serum 5-HT levels decreased while DA,TNF-α,and IL-1 β levels increased(P＜0.05);striatal 5-HT,DA,cAMP,p-PKA/PKA,and p-CREB/CREB protein levels decreased,while TNF-α,IL-1 β,and ROS levels increased(P＜0.05).Compared with the model group,rats in the forsythoside group exhibited reduced motor behaviour and stereotypy scores(P＜0.05),improved striatal neuronal pathology,elevated serum 5-HT levels with reduced DA,TNF-α,and IL-1β levels(P＜0.05),increased striatal 5-HT,DA,cAMP,p-PKA/PKA,and p-CREB/CREB protein levels with reduced TNF-α,IL-1 β,and ROS levels(P＜0.05).H-89 reversed the ameliorative effects of forsythoside in TS rats(P＜0.05).Conclusion:Phillyrin can im-prove the behavior and neuroinflammation in TS rats,and its mechanism may be related to the regulation of the cAMP/PKA signaling pathway.
宋玉静;宋丽娜;张兰;陈梦鹤;康圆圆;段晶晶
河北省定州市人民医院儿科,河北 定州 073000河北省定州市人民医院儿科,河北 定州 073000河北省定州市人民医院儿科,河北 定州 073000河北省盐山县人民医院,河北 沧州 061300河北省盐山县人民医院,河北 沧州 061300河北省石家庄市妇幼保健院儿保科,河北 石家庄 050000
多发性抽动症连翘苷神经-炎症纹状体cAMP/PKA信号通路
Tourette syndromePhillyrinNeuroinflammationStriatumcAMP/PKA signa-ling pathway
《河北医学》 2026 (3)
397-402,6
河北省中医药类科学研究课题计划项目,(编号:2024199)
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