圣·约翰草提取物片对创伤后应激障碍模型小鼠恐惧和焦虑行为的改善作用

Improvement effect of extract of St.John′s wort tablets on fear and anxiety behavior of post-traumatic stress disorder model mice

目的研究圣·约翰草提取物片(ESJWT)对短暂电击所致创伤后应激障碍(PTSD)模型小鼠行为的影响,并探讨ESJWT防治PTSD的可能性。方法 48只雄性C57BL/6小鼠随机分为正常对照组、模型组、舍曲林(15 mg·kg-1)和ESJWT(25 mg·kg^(-1))治疗组,每组12只;除正常对照组外其余各组小鼠连续2 d给予不可逃避的足底电击(0.8 mA,持续10 s,间隔10 s,每天15次),实验前1 h药物处理组小鼠分别ig给予盐酸舍曲林和ESJWT,每天1次,持续18 d。第3,8和15天测量小鼠僵住时间百分比和粪便量,于第16,17和18天依次对小鼠进行旷场实验、高架十字迷宫实验和爬梯实验。行为学实验结束后用ELISA测定小鼠血清去甲肾上腺素(NE)和5-羟色胺(5-HT)含量。结果与正常对照组相比,模型组小鼠僵住时间百分比和粪便量显著增加(P<0.01),进入旷场中央区域的次数和时间均显著降低(P<0.01),进入高架十字迷宫开臂的次数和时间均显著降低(P<0.01),爬梯实验中小鼠爬梯次数无显著性差异,但站立次数明显增加(P<0.01),提示PTSD模型制备成功。与模型组相比,舍曲林和ESJWT均能有效改善上述模型小鼠PTSD样行为(P<0.05,P<0.01),其中ESJWT治疗组小鼠在条件恐惧环境下粪便量较模型组显著减少(P<0.01)。各组小鼠血清NE和5-HT含量均无显著性差异。结论 ESJWT可有效改善PTSD模型小鼠的恐惧和焦虑等行为,有可能用于PTSD治疗。

OBJECTIVE To investigate the effect of extract of St.John′s wort tablets（ESJWT） on post-traumatic stress disorder（PTSD） in a mouse model and explore possible avenues for the treatment of PTSD.METHODS Forty-eight C57 BL/6 male mice were randomly divided into 4 groups：normal control group,model group,sertraline and ESJWT treatment groups,with 12 mice in each group.Except the normal control group,all the mice were treated with fifteen intermittent inescapable foot-shocks（intensity：0.8 mA; interval：10 s; duration：10 s） for 2 d.Sertraline 15 mg·kg^-1 and ESJWT 25 mg·kg^-1 were ig given one hour before foot-shocks repectively,once a day,for 18 d.Then,contextual freezing and fecal pellet were tested on the 3 rd,8 thand 15 thdays.In addition,open field test,elevated plus maze test and staircase test were performed on the 16 th,17 thand18 thdays,respectively.Here,the day mice were subjected to short foot-shocks was defined as the 1 stday.The serum contents of norepinephrine（NE） and 5-hydroxytryptamine（5-HT） were evaluated using ELISA after behavior tests.RESULTS Compared with normal control group,the freezing time and the number of fecal pellet in model group were significantly increased（P〈0.01）.Meanwhile,the time and number of entries into the central open field and open arm were decreased（P〈0.01）.The above experiments indicated that the mouse model of PTSD was established successful y.Compared with model group,both sertraline and ESJWT extract showed anti-PTSD effect,with the decreased percentage of freezing time（P〈0.05,P〈0.01）.ESJWT extract treatment also reduced the amount of fecal pellet（P〈0.01）.However,no significant changes of the contents of NE and 5-HT in any group were seen.CONCLUSION ESJWT has anti-PTSD effect in the mouse model,which might be used for the treatment of PTSD.