小檗胺对脂多糖诱导小鼠抑郁样行为和学习记忆的调节作用  

Modulation of lipopolysaccharide-induced depressive-like behaviors and learning memory in mice by berbamine

作　　者：何昂 陈清杰[2] 黄翠萍[3] 吴宁华 HE Ang;CHEN Qing-jie;HUANG Cui-ping;WU Ning-hua(School of Pharmacy,Faculty of Medicine,Hubei University of Science and Technology,Xianning Hubei 437100,China;Hubei Key Laboratory of Diabetes and Angiopathy,Hubei University of Science and Technology,Xianning Hubei 437100,China;the Second Affiliated Hospital of Hubei University of Science and Technology,Xianning Hubei 437099,China;School of Basic Medical Sciences,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,湖北咸宁437100 [2]湖北科技学院糖尿病心脑血管病变湖北省重点实验室,湖北咸宁437100 [3]湖北科技学院附属第二医院,湖北咸宁437099 [4]湖北科技学院基础医学院,湖北咸宁437100

出　　处：《中国药理学通报》2024年第6期1042-1048,共7页Chinese Pharmacological Bulletin

基　　金：湖北省教育厅科学研究计划指导性项目(No B2022191);大学生创新训练项目(S202210927025);湖北省自然科学基金项目(2022CFB287)。

摘　　要：目的探讨小檗胺对LPS诱导慢性神经炎症模型小鼠行为改变的作用及机制。方法连续7 d给予腹腔注射脂多糖的方法建立小鼠神经炎症模型;小檗胺腹腔注射给药治疗;检测各组小鼠行为学、尼氏染色观察小鼠海马病理形态及炎症相关蛋白的表达水平变化。结果与对照组相比,模型组的小鼠海马CA1区、CA3区神经元数量明显减少;在水迷宫实验中,随着接受训练的天数逐渐增加,逃逸潜伏期逐渐增长,目标象限的滞留时间下降;在强迫游泳实验中,模型组小鼠的静止不动时间增加;小鼠血清中的炎症因子的含量增多;小鼠的海马组织中NLRP3及RHOA/ROCK信号通路相关蛋白的表达水平均增加。与模型组相比,通过小檗胺给药治疗的干预,模型组小鼠海马CA1和CA3区神经元数量增多,同时,随着训练天数的增加,逃逸潜伏期逐渐减少,而目标象限滞留时间增多;强迫游泳中模型组小鼠的静止时间减少;小鼠血清炎症因子含量减少;小鼠海马组织中NLRP3及RHOA/ROCK信号通路相关蛋白的表达水平均降低。结论小檗胺可以改善脂多糖诱导的小鼠抑郁样行为和调节学习记忆,可能与NLRP3和RHOA/ROCK信号通路有关。Aim To investigate the effects of berbamine on behavioral changes in LPS-induced chronic neuroinflammation model mice and the related mechanisms.Methods By injecting lipopolysaccharide intraperitoneally for seven days in a row,berbamine was given intraperitoneally as a treatment;the behavioral studies of mice in each group were identified;Nissen staining was used to observe the changes in the pathological morphology of the mouse hippocampus and the expression levels of inflammation-related proteins.These procedures established a mouse neuroinflammation model.Results The number of neurons in the model group′s hippocampal CA1 and CA3 regions was significantly smaller than that in the control group.In the water maze experiment,as the number of training days grew,the model group′s escape latency increased and its retention time in the target quadrant dropped.The immobilization period of the model group mice increased during the forced swimming exercise.Serum levels of inflammatory factors such as IL-1β,IL-6,and TNF-αlevels were also higher.The hippocampus tissue of the mice in the model group had higher levels of NLRP3,ASC,caspase-1,IL-18,ROCK1,ROCK2 expression,and RHOA.When compared to the model group,the administration of berbamine was a therapy intervention.In the meantime,with the number of training days increased,the target quadrant lag time increased and the escape latency gradually decreased.Additionally,the model group′s mice spent less time resting during forced swimming,and the serum inflammatory factors TNF-α,IL-1β,and IL-6 decreased in mouse hippocampal tissues.Lastly,the expression levels of NLRP3,caspase-1,ASC,IL-1β,ROCK1,ROCK2,and RHOA all decreased in mouse hippocampal tissue.Conclusions The mechanism of action of berbamine,which improves lipopolysaccharide-induced depressive-like behaviors and modifies learning memory in mice,may include the NLRP3 and RHOA/ROCK signaling pathways.

关 键 词：小檗胺 神经炎症 RHOA/ROCK信号通路 NLRP3炎性小体 脂多糖 抑郁症 

分 类 号：R-332[医药卫生] R284.1R322.81R364.5R749.42