抑肝散防治急性应激障碍向创伤后应激障碍发展的作用与机制研究  

Study on the effect and mechanism of Yigan Powder in preventing from the progression of acute stress disorder to post-traumatic stress disorder

作　　者：周桐宇 曹秋实 孙雅琴 卢绮萍 何东初 刘哲 李德顺 ZHOU Tong-yu;CAO Qiu-shi;SUN Ya-qin;LU Qi-ping;HE Dong-chu;LIU Zhe;LI De-shun(School of Basic Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;Central Theater General Hospital of Chinese People's Liberation Army,Wuhan 430070,China)

机构地区：[1]湖北中医药大学基础医学院,湖北武汉430065 [2]中国人民解放军中部战区总医院,湖北武汉430070

出　　处：《时珍国医国药》2025年第3期419-426,共8页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金青年项目(82305082;82305079);中国人民解放军中部战区总医院博士后科研启动基金(BSH013)。

摘　　要：目的评价抑肝散对急性应激障碍(ASD)向创伤后应激障碍(PTSD)发展小鼠模型的防治作用与机制。方法选取雄性C57BL/6J小鼠随机分为正常组、模型组、抑肝散低剂量组、抑肝散高剂量组、盐酸舍曲林组。足底电击制备ASD向PTSD发展小鼠模型。抑肝散低、高剂量组分别给予0.5,1g·kg^(-1)抑肝散,盐酸舍曲林组给予0.01 g·kg^(-1)盐酸舍曲林,正常组与模型组给予生理盐水,每天灌胃1次,连续27d。在急、慢性期分别行旷场实验、创伤线索回避实验、情景恐惧实验、行为特征分析评价小鼠的行为学变化;苏木素-伊红(HE)染色观察小鼠海马形态变化;免疫荧光双标染色检测小鼠海马干细胞增殖分化情况。结果与正常组比较,模型组小鼠急、慢性期旷场实验的中心区域运动距离百分比、探索物体时间减少,僵直时间增加(P<0.05,P<0.01),其中探索物体时间和僵直时间的急、慢性期存在正相关性(P<0.05);海马组织细胞形态异常,结构松散,数量减少;海马干细胞增殖、分化减少(P<0.01)。给药后,与模型组比较,抑肝散低剂量组、抑肝散高剂量组、盐酸舍曲林组小鼠旷场实验的中心区域运动距离百分比增加(P<0.05,P<0.01),抑肝散低剂量组小鼠探索物体时间增加(P<0.05),抑肝散高剂量组小鼠僵直时间减少(P<0.05),海马组织细胞形态、结构恢复,数量增多;抑肝散高剂量组与盐酸舍曲林组小鼠海马干细胞增殖及分化增多,且抑肝散高剂量组较盐酸舍曲林组更多(P<0.01)。结论抑肝散可促进ASD向PTSD发展小鼠的海马神经元再生,保护神经元结构与功能,改善小鼠的焦虑、回避行为和再体验行为,防治ASD向PTSD发展。Objective To evaluate the preventive effect and mechanism of Yigan Powder(YGP)on the development of acute stress disorder(ASD)to post-traumatic stress disorder(PTSD)in mice.Methods Male C57BL/6J mice were randomly divided into the normal,model,YGP low-dose,YGP high-dose,and sertraline hydrochloride groups.A mouse model of ASD progressing to PTSD was established using foot shock.The YGP low and high-dose groups were administered 0.5 and 1g·kg^(-1)of YGP respectively,while the sertraline hydrochloride group received 0.01g·kg^(-1)of sertraline hydrochloride.The normal and model groups were given normal saline.All treatments were gavaged once daily for 27 consecutive days.Behavioral changes in mice were evaluated in the acute and chronic phases using the open-field test,trauma cue avoidance test,contextual fear test,and behavioral characteristic analysis.Hematoxylin-eosin(HE)staining was used to observe morphological changes in the mouse hippocampus.Immunofluorescence double-labeling staining was employed to detect the proliferation and differentiation of hippocampal stem cells in mice.Results Compared with the normal group,the model group mice showed a decreased percentage of central area movement distance in the open-field test,reduced time spent exploring objects,and increased immobility time during both the acute and chronic phases(P<0.05,P<0.01).There was a positive correlation between the time spent exploring objects and immobility time during the acute and chronic phases(P<0.05).The hippocampal tissue cells exhibited abnormal morphology,loose structure,and reduced cell numbers.The proliferation and differentiation of hippocampal stem cells were also reduced(P<0.01).After drug administration,compared with the model group,the YGP low-dose,YGP high-dose,and sertraline hydrochloride groups showed an increased percentage of central area movement distance in the open-field test(P<0.05,P<0.01).The YGP low-dose group exhibited increased time spent exploring objects(P<0.05),while the YGP high-dose group showed reduce

关 键 词：急性应激障碍 创伤后应激障碍 抑肝散 海马 神经元再生 

分 类 号：R285.5[医药卫生—中药学]