天麻多糖对阿尔茨海默症小鼠焦虑行为及记忆功能的影响

Effect of Gastrodia elata polysaccharide on anxiety-like and learning/memory behaviors in AD mouse models

目的构建D-半乳糖(D-gal)联合三氯化铝(AlCl 3)致阿尔茨海默病(AD)小鼠模型,探讨天麻多糖(GEP)对AD小鼠焦虑行为及条件恐惧记忆能力的影响。方法采用皮下注射D-gal(60 mg/kg)联合灌胃AlCl 3(5 mg/kg)构建AD小鼠模型,给予小鼠GEP(50、100、150 mg/kg)进行干预。AD小鼠分别于给药第7、18天进行高架十字迷宫实验(EPMT)、旷场实验(OFT)和恐惧箱实验(FCT),评价GEP对AD小鼠焦虑行为和条件暗示性记忆能力的改善作用。结果与空白组相比,模型组小鼠进入高架十字迷宫开臂的时间比(P<0.001)和次数比显著减少(P<0.01),在旷场实验中心区运动距离减少(P<0.05),活动时间缩短(P<0.01);分别给予GEP 50、100、150 mg/kg后,AD小鼠进入高架十字迷宫开臂的时间比(P<0.001)和次数比(P<0.01)增加,进入旷场实验中心区的活动时间延长,且运动距离增加(P<0.05),提示GEP可改善AD小鼠的焦虑样行为。恐惧箱实验结果显示,与空白组相比,模型组小鼠在恐惧箱内的僵直时间和僵直次数增加(P<0.001)。与模型组相比,GEP减少AD小鼠在恐惧箱内的僵直时间和次数(P<0.001),且呈剂量依赖性,提示GEP能改善AD小鼠的学习记忆能力。结论GEP能改善AD模型小鼠的焦虑行为和记忆功能,但其具体作用机制尚待进一步研究。

Objective An AD model induced by D-gal combined with AlCl 3 was performed to explore whether GEP ameliorates the anxiety-like and learning/memory behaviors in mice.Methods AD was induced in adult male Kunming mice with D-gal(60 mg/kg,b.w.,s.c.)and AlCl 3(5 mg/kg,b.w.,i.g.)for 42 days.42 days after induction,mice were treated with GEP(50,100 and 150 mg/kg,b.w.,i.g.)for 18 days,respectively.Behaviors tests were carried out on days 7 and 18 of dosing to examine anxiety-like cognitive behaviors,and learning and memory behaviors by using the EPMT,OFT,and FCT tests.Results Compared with the blank group,the time ratio(P<0.001)and frequency ratio(P<0.01)of mice in the model group entering the open arm of the elevated cross maze were significantly reduced;meanwhile,the movement distance(P<0.05)and residence time(P<0.01)of mice were also reduced.The administrated of GEP at doses of 50,100 and 150 mg/kg dramatically ameliorated D-gal combined with AlCl 3 induced anxiety-like behaviors in mice.Briefly,GEP increased the time ratio and frequency ratio(P<0.001)of mice entering the elevated cross maze,and also increased the movement distance and residence time(P<0.05)of mice,indicating that GEP improved the anxiety-like behaviors of AD mice.The FCT results have shown that,compared with the blank group,the freezing time and freezing frequency of mice in the model group increased obviously(P<0.001).While GEP notably reduced the freezing time(P<0.001),and freezing frequency(P<0.001)of mice in a fear box,indicating that GEP improved the conditioned fear memory of mice.Conclusion Our findings proved that GEP is beneficial in alleviating anxiety-like behavior,and improving learning and memory in the AD mouse model.However,the related underlying mechanism needs to be further elucidated.