当归芍药散对慢性束缚应激模型大鼠海马NMDAR1、GluR2及BDNF表达和抑郁样行为的影响  

Effects of Danggui Shaoyao Powder on the expressions of NMDAR1,GluR2,BDNF in hippocampus and depressive-like behavior of chronic immobilization stress model rats

作　　者：辛泰然 张碧涛 王浩[1] 李红红 丁跃玲[1] 王少贤[1,2] XIN Tai-ran;ZHANG Bi-tao;WANG Hao;LI Hong-hong;DING Yue-ling;WANG Shao-xian(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Key Laboratory of Integrated Chinese and Western Medicine for Lung Disease Research,Shijiazhuang 050091,China)

机构地区：[1]河北中医学院,石家庄050200 [2]河北省中西医结合肺病研究重点实验室,石家庄050091

出　　处：《中华中医药杂志》2023年第3期1003-1008,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81673881,No.81202644);河北省自然科学基金项目(No.H2016423046);河北省高层次人才资助项目(No.A201901038);河北中医学院研究生创新立项项目(No.XCXZZSS2021004)。

摘　　要：目的:观察当归芍药散对慢性束缚应激模型大鼠海马谷氨酸受体N-甲基-D-天冬氨酸受体1(NMDAR1)、谷氨酸受体2(GluR2)以及脑源性神经营养因子(BDNF)表达和抑郁样行为的影响。方法:60只SD大鼠随机分为空白组、模型组、氟西汀组、当归芍药散组,每组15只。除空白组外,其余各组采用束缚方式制备慢性应激模型,当归芍药散组大鼠应激同时灌胃当归芍药散混悬液13.44 g·kg^(-1)·d^(-1),氟西汀组应激同时灌胃氟西汀水溶液2 mg·kg^(-1)·d^(-1),空白组与模型组灌胃等体积0.9%氯化钠溶液,1次/d,实验21 d。采用糖水消耗实验、高架十字迷宫实验评价大鼠行为学变化,尼氏染色法观察大鼠海马神经元病理变化,免疫组化法和qRT-PCR法分别检测大鼠海马CA1区NMDAR1、GluR2、BDNF蛋白及mRNA的表达。结果:与空白组比较,模型组大鼠体质量降低,糖水消耗率、高架十字迷宫实验开放臂停留时间及进入次数显著减少(P<0.05),海马CA1区尼氏小体数量、GluR2与BDNF蛋白及mRNA表达均显著降低(P<0.05),而NMDAR1蛋白及mRNA表达显著升高(P<0.05)。与模型组比较,当归芍药散组大鼠体质量、糖水消耗率、高架十字迷宫实验开放臂停留时间及进入次数均显著增加(P<0.05),海马CA1区尼氏小体数量、GluR2与BDNF蛋白及mRNA表达均显著升高(P<0.05),而NMDAR1蛋白及mRNA表达降低(P<0.05);Pearson相关分析表明,大鼠糖水消耗率、开放臂进入次数、开放臂停留时间、尼氏小体与其海马CA1区GluR2、BDNF mRNA表达呈正相关(P<0.05,P<0.01),与NMDAR1 mRNA表达呈负相关(P<0.05,P<0.01)。结论:慢性束缚应激可导致大鼠出现抑郁样行为和海马NMDAR1、GluR2、BDNF表达的明显变化,当归芍药散可能通过抑制应激大鼠海马CA1区NMDAR1表达,提高GluR2、BDNF的表达,发挥一定的抗抑郁作用。Objective:To observe the effects of Danggui Shaoyao Powder on the hippocampal glutamate receptor NMDAR1,GluR2 and BDNF expression,and depressive-like behavior.Methods:A total of 60 SD rats were randomly divided into control group,model group,fluoxetine group,and Danggui Shaoyao Powder group,with 15 rats in each group.Except for the control group,the rest of the groups used chronic immobilization stress to make chronic stress model.The rats of Danggui Shaoyao Powder group were given Danggui Shaoyao Powder suspension 13.44 g·kg^(-1)·d^(-1),and the rats of fluoxetine group were given fluoxetine aqueous solution 2 g·kg^(-1)·d^(-1),the rats of control group and model group were given equal volume of 0.9%sodium chloride solution.All the medicine were intragastrically administrated once a day,for 21 consecutive days.Sucrose Sonsumption Test and Elevated Plus Maze Test were used to evaluate the behavior changes of rats,Nissl’s staining were used to observe the pathological changes of hippocampal neurons of rats,immunohistochemistry and qRT-PCR methods were used to detect the expressions of NMDAR1,GluR2 and BDNF protein and mRNA in the CA1 regions of rats’hippocampi.Results:Compared with the control group,the weight gain of rats in the model group was slow,the sucrose consumption rate,the residence time in the open arms,and the number of entries within 5 min of Elevated Plus Maze Test were significantly reduced(P<0.05);the number of Nissl’s bodies in the CA1 regions of hippocampi,and the expressions of GluR2 and BDNF protein and mRNA decreased significantly(P<0.05),while the expressions of NMDAR1 increased significantly(P<0.05).Compared with the model group,Danggui Shaoyao Powder group had significantly increased body weight,sucrose consumption rate,and the residence time in the open arms,the number of entries within 5 min of Elevated Plus Maze Test increased significantly(P<0.05),the number of Nissl’s bodies in the hippocampal CA1 regions,the expressions of GluR2 and BDNF protein and mRNA increased significan

关 键 词：慢性束缚应激 抑郁 当归芍药散 谷氨酸受体 脑源性神经营养因子 

分 类 号：R285.5[医药卫生—中药学]