仙茅苷对抗PTSD诱导的小鼠海马炎症反应机制

Mechanism of curculigoside against PTSD-induced inflammatory response in mouse hippocampus

仙茅苷(CUR)是仙茅的主要成分,具有多种生物活性。然而,CUR能否调控创伤后应激障碍(PTSD)诱导的小鼠海马炎症尚不清楚。采用改良的单次延长应激和电击(SPS&S)小鼠模型,探讨仙茅苷通过核转录因子κB(NF-κB)通路抑制PTSD小鼠海马神经炎症的作用机制。结果显示:与SPS&S模型组相比,仙茅苷能够显著降低PTSD小鼠在恐惧消退中的凝滞时间(P<0.05),增加其在旷场中心区域的运动时间与距离(P<0.05),并增加其在高架十字迷宫中进入开放臂的次数(P<0.05);同时,仙茅苷能降低PTSD小鼠血清中促炎因子TNF-α与IL-1β的水平(P<0.05),改善其海马CA1区神经细胞的病理变化,降低其海马组织中NF-κB、NLRP3、Caspase-1的表达水平(P<0.05)。表明仙茅苷改善SPS&S诱导的PTSD小鼠焦虑样行为,可能是通过抑制NF-κB介导的神经炎症通路发挥作用。

Curculigoside(CUR)is the main component of Curculigo and has various biological activities.However,it is not clear whether CUR inhibits post-traumatic stress disorder(PTSD)-induced inflammation in the hippocampus of mice.In this study,a modified mouse model of single prolonged stress and electrical stimulation(SPS&S)was established to investigate the effect of curculigoside on neuroinflammation in the hippocampus of SPS&S-treated mice from the prospective of nuclear factor kappa-B(NF-κB)pathway.The results showed that,compared with that of SPS&S group,CUR significantly reduced the freezing time of PTSD mice during fear extinction(P<0.05).It increased the movement time and distance in the central area in the open field test(P<0.05),and increased the number of open arms in the Elevated Plus Maze Test(P<0.05).In addition,compared with that of SPS&S group,CUR decreased the levels of TNF-αand IL-1βin serum of PTSD mice(P<0.05).It improved the pathological changes in CA1 regions of the hippocampus,and decreased hippocampal expressions of NF-κB,NLRP3,and Caspase-1(P<0.05).These data implicated that CUR improved PTSD-like behaviors in mice,which might be related to the regulation of NF-κB-dependent neuroinflammation.