中文摘要：

目的评价小鼠海马糖原合成酶激酶3β（GSK3β）过表达对小补心汤总黄酮（XBXT-2）抗抑郁和抗焦虑作用的影响。方法小鼠海马立体定位微注射包装有GSK3β（S9A）突变型基因的腺相关病毒（AAV）制备小鼠GSK3β过表达模型,3周后采用Western蛋白印迹法检测GSK3β和磷酸化GSK3β（S9）〔pGSK3β（S9）〕含量,采用开场实验检测小鼠自发活动。而后将空载体AAV组和GSK3β过表达组小鼠各自分为给药组和溶剂组,分别ig给予XBXT-2 100 mg·kg~（-1）或同体积蒸馏水,每天1次,分别于给药14和16 d采用悬尾实验和强迫游泳实验检测小鼠抑郁样行为,18和20 d采用高架十字迷宫实验和爬梯实验检测小鼠焦虑样行为。结果 Western蛋白印迹法检测结果显示,与AAV组相比,GSK3β过表达组小鼠海马GSK3β含量显著升高（P〈0.01）,p-GSK3β（S9）含量无显著性差异。在开场实验中,GSK3β过表达组与AAV组间小鼠跨格次数和站立次数无显著差异。在小鼠悬尾和强迫游泳实验中,AAV＋XBXT-2组与AAV组比较,小鼠不动时间显著缩短（P〈0.05,P〈0.01）;GSK3β过表达＋XBXT-2组与GSK3β过表达组比较,小鼠不动时间无明显差异。在高架十字迷宫实验中,与AAV组比较,AAV＋XBXT-2组小鼠进入开臂次数百分比和开臂停留时间百分比显著增加（P〈0.01,P〈0.05）;与GSK3β过表达组比较,GSK3β过表达＋XBXT-2组小鼠上述行为指标无明显改变。在爬梯实验中,AAV＋XBXT-2组比AAV组小鼠爬梯站立次数显著减少（P〈0.05）;GSK3β过表达＋XBXT-2组与GSK3β过表达组比较,小鼠站立次数无明显差异。结论海马脑区GSK3β过表达可取消XBXT-2在小鼠悬尾和强迫游泳实验中的抗抑郁作用及在高架十字迷宫实验和爬梯实验中的抗焦虑作用。

英文摘要：

OBJECTIVE To study the influence of glycogen synthase kinase3β（GSK3β） over expression in the hippocampus on the antidepressant and anxiolytic effects of total flavoids from Xiaobuxin Tang（XBXT-2）. METHODS Adeno-associated virus containing GSK3β（S9A） mutation was microinjected into the hippocampus. After three weeks of recovery, GSK3β and p-GSK3β were detected by Western blotting, and open field test（OFT） was used to evaluate the locomotor activity. Then, AAV group and GSK3β over expression group were divided into administration group and solvent group, respectively.XBXT-2（100 mg·kg-1） and solvent were ig administered chronically. After 14 d and 16 d of administration, the tail suspension test（TST） and forced swimming test（FST） were used to investigate the influence of GSK3β over expression on the antidepressant effect of XBXT-2, respectively. After 18 d and 20 d of administration, the elevated plus maze test（EPMT） and staircase test（ST） were used to investigate the influence of GSK3β over expression on the anxiolytic effects of XBXT-2, respectively. RESULTS Western blotting analysis showed that the protein level of GSK3β increased significantly in GSK3β over expression group（P〈0.01） compared with AAV group, but there was no significant difference in p-GSK3β. In OFT, the number of crossings and rearings showed no difference between AAV group and GSK3β over expression group. The results of TST and FST showed that compared with AAV group, the immobility time was significantly reduced in AAV ＋ XBXT-2 group（P〈0.05, P〈0.01）, but compared with GSK3β over expression group, the immobility time showed no difference in GSK3β over expression ＋XBXT-2 group. In EPMT, compared with AAV group, the percentage of entrances and time into open arms in AAV＋XBXT-2 group was significantly increased（P〈0.01, P〈0.05）, but compared with GSK3βover expression group, these indexes showed no difference in GSK3β over expression＋XBXT-2 group.In ST, compared with A