摘要
目的:通过观察固本健脑液对AD大鼠学习记忆、生物钟基因及海马Aβ含量的影响,探索该方改善学习记忆和睡眠障碍的可能机制。方法:实验大鼠随机分为正常组、模型组、药物高、中、低剂量组。自主活动分析仪检测各组大鼠的自主活动情况;Morris水迷宫检测各组大鼠学习记忆能力;ELISA检测大鼠海马Aβ1-40和Aβ1-42含量;免疫组化检测SCN中Bmal1和Clock的蛋白表达水平。结果:自主活动结果显示模型组大鼠活动时间较空白组呈现出显著的增加(P<0.01);各给药组出现活动时间减少(P<0.05)。Morris水迷宫结果显示,模型组大鼠较空白组逃避潜伏期显著延长,目标象限游泳时间百分比显著下降(P<0.01);各观察组逃避潜伏期显著缩短,目标象限游泳时间百分比显著上升(P<0.01,P<0.05);ELISA结果显示,模型组大鼠海马Aβ1-40和Aβ1-42含量较空白组显著增多(P<0.01),固本健脑液中、高剂量组海马Aβ1-40和Aβ1-42含量显著下降(P<0.01)。免疫组化结果:模型组大鼠SCN中Bmal1和Clock表达水平较空白组下降(P<0.01),给药后,各组大鼠SCN中Bmal1和Clock表达上升(P<0.05)。结论:结果显示AD大鼠存在一定程度的昼夜节律紊乱且生物钟节律基因表达降低,固本健脑液干预后可改善痴呆大鼠的昼夜节律紊乱及海马Aβ的异常表达,其机制则可能与固本健脑液上调Bmal1、Clock表达有关。
Objective:To explore the possible mechanisms of improving learning and memory and sleep disorders were explored by observing the effects of Root-Securing and Brain-Fortifying Liquid(RSBFL)on learning and memory,biological clock gene and the content of hippocampal Aβin AD model rats.Methods:The rats were randomly divided into a normal group,a model group,a high,a medium and a low dose groups.The autonomic activity of rats in each group was detected by autonomic activity analysis system.Morris water maze was used to test the learning and memory ability of rats in each group.ELISA was used to detect the contents of Aβ1-40 and Aβ1-42 in the hippocampus of rats.Immunohistochemistry was used to detect the protein expression levels of Bmal1 and Clock in SCN.Results:The results of autonomic activity showed that compared with the normal group,the activity time of rats in the model group increased significantly(P<0.01);compared with the model group,the activity time of rats in each drug group decreased to different degrees(P<0.05).Morris water maze results showed that compared with the blank control group,the escape latency period of rats in the model group was significantly prolonged,and the percentage of target quadrant swimming time was significantly decreased,with statistically significant differences(P<0.01);compared with the model group,the evasive incubation period of each treatment group was significantly shortened,and the percentage of target quadrant swimming time was significantly increased,with statistically significant differences(P<0.01,P<0.05).ELISA results showed that compared with the blank control group,the contents of Aβ1-40 and Aβ1-42 in hippocampus were significantly increased in the model group(P<0.01).Compared with the model group,the contents of Aβ1-40 and Aβ1-42 in hippocampus of rats in the medium and high dose RSBFL groups decreased significantly(P<0.01).Immunohistochemical detection results:the expression levels of Bmal1 and Clock in SCN of rats in the model group decreased(P<0.01)compared with that in the blank control group.After administration,HE expression levels of Bmal1 and Clock in SCN of rats in each group increased(P<0.05).Conclusion:The results of this study show the AD model rats had a certain degree of circadian rhythm disorder and the expression of circadian rhythm gene was decreased.The intervention of RSBFL can improve circadian rhythm disorders and abnormal expression of Aβin hippocampus of dementia rats,and the mechanism may be related to the upregulation of Bmal1 and Clock expression of RSBFL.
作者
张誉丹
毛剑琴
袁林
袁德培
ZHANG Yudan;MAO Jianqin;YUAN Lin;YUAN Depei(School of Basic Medical Sciences,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Minzu University for Medical Department/Hubei University for Nationalities Rheumatic Disease Occurrence and Intervention Hubei Provincial Key Laboratory,Enshi 445000,China)
出处
《世界中医药》
CAS
2020年第23期3634-3638,3645,共6页
World Chinese Medicine
基金
国家自然科学基金项目(81860811)——基于caveolin-1通过NMDAR/ERK/CREB通路影响突触发育及重塑探讨探讨固本健脑液对AD的作用及机制。
