河北医学2026,Vol.32Issue(3):397-402,6.DOI:10.3969/j.issn.1006-6233.2026.03.07
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
An Exploration of the Effect of Phillyrin on Neuroinflammation in Tourette Syndrome via the cAMP/PKA Signaling Pathway
摘要
Abstract
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.关键词
多发性抽动症/连翘苷/神经-炎症/纹状体/cAMP/PKA信号通路Key words
Tourette syndrome/Phillyrin/Neuroinflammation/Striatum/cAMP/PKA signa-ling pathway引用本文复制引用
宋玉静,宋丽娜,张兰,陈梦鹤,康圆圆,段晶晶..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[J].河北医学,2026,32(3):397-402,6.基金项目
河北省中医药类科学研究课题计划项目,(编号:2024199) (编号:2024199)