中药Ⅰ号方对APP/PS1双转基因AD小鼠模型行为和精神症状的影响

摘要

Objective To investigate the effects of a Chinese traditional prescription PN-1 on behavioral and psychological symptoms in APP/PS1 transgenic mouse models of Alzheimer' s disease (AD). Methods Mouse models at 5 months of age were randomly divided into mode) group (vehicle) , Aricept administration group (2 mg/kg) , PN-1 at low (0.6 g/kg), middle (1.2 g/kg) and high (2.4 g/kg) doses. The wild-type littermates were chosen as normal control group (WT). The 16 mice (8 males and 8 females) in each group were given once every day by intragastric administration of PN-1, Aricept or water for 3 months. The body weight and the amount of water drinking and food intakes were measured before administration and every two weeks during administration. After the drug administration, a battery of behavioral tests including social interaction, open field, rota-rod and sucrose preference were performed. Results During the administration, no changes in body weight and food/water intake were detected in PN-1 -treated mice, compared with the age-matched wild-type control and vehicle mice (P > 0.05). Compared with the mice in the vehicle group, social interaction test showed reduced attack, chasing and sniffing in the PN-1 -treated groups ( P < 0. 05). The mice in the PN-1 -treated groups showed decreased spontaneous motor activity (P < 0. 05) , highly mobile duration (P < 0. 05) , frequency to center zone (P < 0. 05) and increased frequency of grooming in the open field test. Rota-rod test exhibited increased time spent on rod (P <0. 05) for the PN-1-treated mice. In addition, increased sucrose consumption was also found in the PN-1-treated group, however, no statistically significant difference was found compared with the vehicle group (P >0. 05). Conclusions PN-1-treatment can ameliorate many non-cognitive behaviors and psychological symptoms in the APP/PS1 transgenic mouse models, including rescued hyperactive social interaction, spontaneous motor activity, improved ability to learn balance , and reduced anxiety, irritability and other psychological symptoms.%目的 研究中药Ⅰ号方( PN-1)对APP/PS1双转基因AD小鼠模型行为和精神症状的影响.方法将5月龄的APP/PS1双转基因AD小鼠随机分为模型组(vehicle)、安理申(Aricept)治疗组(2 mg/kg)、PN-1低(0.6g/kg)、中(1.2 g/kg)、高(2.4 g/kg)剂量组,并以同窝阴性的C57B L/6小鼠作为正常对照组(WT),每组16只,雌雄各半.绘药组小鼠每天灌胃给药1次,同时模型组及正常组小鼠给予等体积的双蒸水灌胃.给药前称量小鼠初始体重、摄食量和饮水量；给药期间,每两周逐只称量体重一次,同时称量并计算摄食量和饮水量.给药3个月后(8月龄)依次进行社会互动行为检测、旷场实验、Rota-rod实验和蔗糖饮水实验来观察PN-1对APP/PS1小鼠行为和精神症状的作用.结果 给药期间,相同月龄下各组小鼠间的体重、摄食和饮水均无显著性差异(P＞0.05).社会互动行为检测发现PN-1显著减少模型小鼠异常增多的攻击、追逐和嗅闻次数(P＜0.05).旷场实验结果显示,PN-1能够减少转基因小鼠水平和垂直方向的运动(P＜0.05)和高速运动时间(P＜0.05),同时减少其进入中心区域的探究次数(P＜0.05)并增加其修饰次数(P＜0.05).Rota-rod实验结果发现,PN-1能够增加转基因小鼠在滚轴上停留的时间(P＜0.05).蔗糖饮水实验结果显示,给予PN-1的转基因小鼠蔗糖偏嗜度有增高趋势,但与模型组相比并无显著性差异(P＞0.05).结论 PN-1能够改善APP/PS1双转基因小鼠的社会互动行为、减少过度增强的运动能力和探究行为,提高其耐力和平衡学习能力,并减轻其焦虑、烦躁、易激惹等精神症状.