酸枣仁汤对6月龄APP/PS1双转基因痴呆小鼠昼夜节律及视交叉上核节律基因m RNA表达的影响

Effects of Suanzaoren Decoction on circadian rhythm and expression of clock gene mRNA in suprachiasmatic nucleus of 6-month-old APP/PS1 double transgenic mice

目的:观察酸枣仁汤对6月龄APP/PS1双转基因痴呆小鼠昼夜节律及视交叉上核(SCN)节律基因表达的影响。方法:将小鼠随机分为空白组,模型组,多奈哌齐组,酸枣仁汤低、高剂量组。给予对应的药物后,用自发活动实验视频分析系统记录小鼠自主活动时间,采用Real time-PCR检测SCN中Per1、Cry1、Clock、Bmal1mRNA表达水平。结果:与空白组比较,APP/PS1组小鼠光照环境活动时间、总活动时间显著增加(P<0.01)。与空白组比较,模型组小鼠光照环境活动时间、黑暗环境活动时间和总活动时间显著增加(P<0.01);与模型组比较,多奈哌齐组、酸枣仁汤低剂量组和酸枣仁汤高剂量组小鼠光照环境活动时间、黑暗环境活动时间和总活动时间显著减少(P<0.05,P<0.01);与多奈哌齐组比较,酸枣仁汤高剂量组小鼠光照环境活动时间、黑暗环境活动时间和总活动时间显著减少(P<0.05)。与空白组比较,模型组小鼠SCN中Per1、Cry1、Clock、Bmal1 mRNA表达水平显著升高(P<0.01);与模型组比较,多奈哌齐组和酸枣仁汤高剂量组小鼠SCN中Per1、Cry1、Clock、Bmal1 mRNA表达水平显著下降(P<0.01),酸枣仁汤低剂量组小鼠SCN中Per1、Clock mRNA表达水平显著下降(P<0.05)。与多奈哌齐组比较,酸枣仁汤低剂量组小鼠SCN中Per1、Cry1、Bmal1 mRNA表达水平显著升高(P<0.05,P<0.01)。结论:6月龄APP/PS1双转基因痴呆小鼠有昼夜节律失调表现,酸枣仁汤可以改善其昼夜节律,其机制可能与其调节小鼠SCN中节律基因Per1、Cry1、Bmal1、Clock mRNA的表达有关。

Objective: To observe the effects of Suanzaoren Decoction on the circadian rhythms of the 6 months old APP/PS1 double transgenic mice and the gene expression of the circadian clock of Suprachiasmatic nucleus(SCN). Methods: The mice were randomly divided into blank group,model group, donepezil group, Suanzaoren Decoction low dose group and Suanzaoren Decoction high dose group. After the appropriate drug was given,the time of spontaneous activity of the rats was recorded with an automotive instrument.The expression of Per1, Cry1, Clock, and Bmal1 in SCN was detected by Real time-PCR. Results: Compared with the blank group,the activity time of light environment and total activity time of the APP/PS1 group were significantly increased(P<0.01). Compared with the blank group,the activity time of light environment,activity time of dark environment and total activity time of the model group were significantly increased(P<0.01). Compared with the model group, the activity time of light environment, activity time of dark environment and total activity time of the donepezil group, Suanzaoren Decoction low dose group and Suanzaoren Decoction high dose group were decreased(P<0.05, P<0.01). Compared with the donepezil group, the activity time of light environment, activity time of dark environment and total activity time of the Suanzaoren Decoction high dose group were decreased(P<0.05). Compared with the blank group, the expression levels of Per1, Cry1, Clock and Bmall mRNA in the SCN of the model group were significantly increased(P<0.01). Compared with the model group, the expression levels of Per1, Cry1, Clock, Bmal1 mRNA in SCN of donepezil group and Suanzaoren Decoction high dose group were significantly decreased(P<0.01), and the expression of Per1 and Clock mRNA in SCN of Suanzaoren Decoction low dose group were decreased(P<0.05). Compared with the donepezil group, the expression levels of Per1, Cry1 and Bmall mRNA in SCN of Suanzaoren Decoction low dose group were increased(P<0.05, P<0.01). Conclusion: The circadian rhythm of 6-month-old APP/PS1 transgenic dementia mice was disordered. Suanzaoren Decoction could change the circadian rhythm of APP/PS1 transgenic dementia mice. The mechanism may be related to its regulation of the expression of the rhythmic genes Per1, Cry1, Bmall and Clock in SCN of mice.