【作者】 吴嘉威； 刘雅洁； 贺晶； 石玉清； 赵百孝；

【Author】 WU Jia-wei;LIU Ya-jie;HE Jing;SHI Yu-qing;ZHAO Bai-xiao;College of Acupuncture and Massage,Beijing University of Chinese Medicine;Xiamen Hospital,Beijing University of Chinese Medicine;

【机构】 北京中医药大学针灸推拿学院； 北京中医药大学厦门医院；

【摘要】 目的:观察艾燃烧生成物干预对APP/PS1小鼠空间记忆能力、嗅觉功能的影响及嗅球、海马组织神经元突触结构的影响,并基于GSK-3β/CREB信号通路探讨艾燃烧生成物的效应途径以及可能的作用机制。方法:将36只4月龄APP/PS1雄性小鼠,随机分为模型组、艾燃烧生成物组、嗅觉障碍后艾燃烧生成物干预组(嗅烟组)和迷迭香精油组(精油组),C57BL/6小鼠作为空白对照组。各组小鼠干预12周后进行水迷宫实验、埋藏食物小球实验,行为学实验结束后牺牲取材,透射电镜观察嗅球及海马神经元突触的超微结构,Western blot法测定嗅球和海马内GSK-3β、CREB、c-fos的蛋白表达变化。结果:Morris水迷宫空间探索实验表明与模型组和嗅烟组相比,艾燃烧生成物组小鼠在目标象限游泳路程、路程占比及游泳时间显著增多(P<0.05);埋藏小球实验结果表明实验干预后,与模型组相比,艾燃烧生成物组小鼠的时间显著减少(P<0.05);透射电子显微镜结果表明,在嗅球和海马组织中,与模型组相比,精油组和艾燃烧生成物组突触数量显著增多(P<0.05);与艾燃烧生成物组相比,嗅烟组突触数量显著减少(P<0.05)。Western-blot结果显示在嗅球和海马组织中,与模型组相比,艾燃烧生成物组小鼠GSK-3β蛋白表达显著减少(P<0.05),CREB蛋白表达显著增多(P<0.05);与艾燃烧生成物组相比,嗅烟组GSK-3β蛋白表达显著增多(P<0.05),CREB和c-fos蛋白表达显著减少(P<0.01)。结论:艾燃烧生成物可以提高APP/PS1模型小鼠的空间记忆能力,改善嗅觉功能,同时能够改善突触结构的受损;进行嗅觉障碍造模后,艾燃烧生成物作用效果减弱,提示艾燃烧生成物可能通过嗅觉传导通路发挥作用,艾燃烧生成物的分子作用途径可能是通过嗅觉传导通路激活GSK-3β/CREB信号通路实现。更多还原

【Abstract】 Objective To observe the effects of moxa combustion products on spatial memory ability,olfactory function and synaptic structure of olfactory bulb and hippocampus in APP/PS1 mice,and explore the mechanism of moxa combustion products.Methods 36 4-month-old APP/PS1 male mice were randomly divided into model group(A),moxa-smoke group(M),moxa-smoke after olfactory impairment group(O) and rosemary essential oil group(R),and C57BL/6 mice served as blank control group(C).Mice in the M group and O group were put into an intervention box with a concentration of 10 to 15 mg/m3 of moxa-smoke,and mice in the R group were put into an intervention box with a concentration of 1%(200 μL) of rosemary essential oil for 20 min/day,6 times/week.After 12 weeks of intervention,water maze experiment and buried food pellet experiment were carried out.The ultrastructure of olfactory bulbs and hippocampal synapses were observed by transmission electron microscopy.The protein expressions of GSK-3β,CREB and c-fos in olfactory bulbs and hippocampal neurons were measured by Western blot.Results Morris water maze space exploration experiment showed that compared with A group and O group,the swimming distance and swimming time of mice in the target quadrant were significantly increased;The results of buried pellets experiment showed that after experimental intervention,compared with the A group,the time of mice in the M group was significantly reduced;Transmission electron microscopy results showed that the number of synapses in the olfactory bulb and hippocampus of R group and M group increased significantly compared with the A group.Western-blot results showed that in the hippocampus and olfactory bulb,the expression of GSK-3β protein of the M group was significantly decreased,while the expression of CREB protein was significantly increased.GSK-3βprotein expression was significantly increased,while CREB and c-fos protein expression was significantly decreased in the O group compared with the M group.Conclusion Moxa combustion product can improve the spatial memory ability and olfactory function of APP/PS1 model mice,and improve the synaptic structure damage.After the modeling of olfactory disorders,the effect of moxa combustion products was weakened,suggesting that moxa combustion products may play a role through the olfactory pathway,and the molecular pathway may be realized through the activation of GSK-3β/CREB signaling pathway through the olfactory pathway.更多还原