益智方改善东莨菪碱致小鼠学习记忆障碍的药理作用研究

Study on the Pharmacological Effect of Yizhi Prescript ion(益智方)on Improving Scopolamine-induced Learning and Memory Impairment in Mice

目的:探究益智方对东莨菪碱致小鼠学习记忆障碍的改善作用。方法:将小鼠随机分为空白组、模型组、益智方低剂量组、益智方中剂量组、益智方高剂量组,每组12只。益智方低、中、高剂量组大鼠灌胃给予益智方溶液,空白组和模型组大鼠灌胃给予等体积纯化水,灌胃体积10 mL/kg,1次/d,连续30 d。除空白组外,其余各组小鼠腹腔注射东莨菪碱(5 mg/kg)制备记忆障碍模型。造模后,采用跳台实验、避暗实验及Morris水迷宫实验等学习记忆相关指标来评价各组小鼠学习记忆能力的变化,并检测小鼠脑组织中乙酰胆碱(ACh)、乙酰胆碱酯酶(AchE)及胆碱乙酰转移酶(ChAT)含量的变化。结果:跳台实验中,与模型组比较,益智方低、中、高剂量组小鼠跳台潜伏期均明显延长(P<0.05或P<0.01),错误次数均明显减少(P<0.01)。避暗实验中,与模型组比较,益智方低、中、高剂量组小鼠小鼠避暗潜伏期明显延长(P<0.01或P<0.05),错误次数显著减少(P<0.01)。Morris水迷宫实验中,与模型组比较,益智方高剂量组小鼠在第1、2、4天找到平台的潜伏期明显缩短(P<0.05);益智方低、中、高剂量组小鼠在第5天找到平台的潜伏期明显缩短(P<0.05);在第6天撤除平台后,与模型组比较,益智方低、中剂量组小鼠逃逸平台滞留时间均明显延长(P<0.05),益智方高剂量组小鼠逃逸平台滞留时间显著延长(P<0.01);益智方低、中、高剂量组小鼠60 s内有效进入次数明显增加(P<0.05或P<0.01)。中、高剂量益智方能显著降低小鼠脑组织中ACh含量(P<0.05),且高剂量益智方能显著提高小鼠脑组织中AchE及ChAT的含量(P<0.05或P<0.01)。结论:益智方可明显改善东莨菪碱致学习记忆障碍模型小鼠的学习记忆能力,其可能通过增加ACh、ChAT含量和降低AchE的含量调节胆碱能通路,进而改善小鼠学习记忆障碍。

Objective:To explore the effect of Yizhi Prescription on scopolamine-induced learning and memory impairment in mice.Methods:The mice were randomly divided into blank group,model group,low-dose Yizhi Prescription group,medium-dose Yizhi Prescription group,high-dose Yizhi Prescription group,with 12 mice in each group.The rats in the low,medium and high-dose groups of Yizhi Prescription were given Yizhi Prescription solution by intragastric administration.The rats in the blank group and the model group were given the same volume of purified water by intragastric administration,with a volume of 10 mL/kg,once a day,for 30 consecutive days.Except for the blank group,mice in the other groups were intraperitoneally injected with scopolamine(5 mg/kg)to prepare memory impairment models.After modeling,the changes of learning and memory ability of mice in each group were evaluated by platform jumping test,dark avoidance test and Morris water maze test,and the changes of acetylcholine(ACh),acetylcholin esterase(AChE)and choline acetyltransferase(ChAT)in mice brain tissue were detected.Results:In the platform jumping test,compared with the model group,the platform jumping latency of mice in the low,medium and high-dose groups of Yizhi Prescription was significantly p rolonged(P<0.05 or P<0.01),and the number of errors was significantly reduced(P<0.01).In the dark avoidance test,compared with the model group,the dark avoidance latency of mice in the low,medium and high-dose groups of Yizhi Prescription was significantly prolonged(P<0.01 or P<0.05),and the number of errors was significantly reduced(P<0.01).In Morris water maze test,compared with the model group,the latency of mice in high dose groups of Yizhi Prescription to find a platform on the 1st,2nd and 4th days was significantly shorter(P<0.05).The incubation period for mice in the low,medium and high-dose groups of Yizhi Prescription to find a plat form on the 5th day was significantly shortened(P<0.05).After the platform was removed on the 6th day,compared with the model group,the escape platform retention time of mice in the low and medium-dose groups of Yizhi Prescription was significantly prolonged(P<0.05),and the retention time of mice escape platform in the high-dose group of Yizhi Prescription was significantly prolonged(P<0.01).The effective entry times of mice in the low,medium and high-dose groups of Yizhi Prescription increased significantly within 60 s(P<0.05 or P<0.01).Medium and high-doses of Yizhi Prescription could significantly reduce the content of ACh in mice brain tissue(P<0.05),and high-doses of Yizhi Prescription could significantly increase the contents of Ach E and Ch AT in mice brain tissue(P<0.05 or P<0.01).Conclusion:Yizhi Prescription can significantly improve the learning and memory ability of scopolamine-induced learning and memory impairment model mice,which may regulate the cholinergic pathway by increasing the content of ACh and Ch AT and reducing the content of Ach E,so as to improving the learning and memory impairment of mice.