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目的观察生慧汤对APP/PS1双转基因痴呆小鼠昼夜节律的影响并探讨其机制。方法将40只5月龄APP/PS1双转基因痴呆小鼠随机分为模型对照组、褪黑素组和生慧汤高、低剂量组,10只相同遗传背景性C57BL/6J小鼠为空白对照组,灌胃给药1个月。用自发活动实验视频分析系统观察小鼠24h内8个时间点的自主活动时间,比较各组8个时点自主活动时间之和(t_(all))、光照时段4个时点自主活动时间之和(t_L)及黑暗时段4个时点自主活动时间之和(t_D),并用Cosinor Matlab软件余弦法分析其时间生物学特征;用Real Time-PCR法检测小鼠下丘脑一系列生物钟基因mRNA的表达。结果与空白组比较,模型组的t_(all)、t_L、t_D均显著性增加(P<0.01);与模型组比较褪黑素组和生慧汤高、低剂量组的t_(all)、t_L均显著性缩短(P<0.05,P<0.01),而t_D无显著性差异(P>0.05)。空白组、褪黑素组和生慧汤高、低剂量组小鼠自主活动时间均能拟合余弦曲线(P<0.05),呈现典型的昼夜节律,其拟合的余弦曲线振幅排序依次为:生慧汤高剂量组>空白组>生慧汤低剂量组>褪黑素组;与空白组比较,模型组Perl mRNA、Cry-1 mRNA、Clock mRNA、Bmall mRNA和Rev-erba mRNA表达均显著性下调(P<0.01)。与模型组比较,褪黑素组Perl mRNA、Cry-1 mRNA、ClockmRNA、Bmall mRNA、Rev-erba mRNA表达均显著性上调(P<0.01);生慧汤高剂量组Perl mRNA、Cry-1 mRNA、Clock mRNA、Bmall mRNA、Rev-erba mRNA表达显著性上调(P<0.01);生慧汤低剂量组Perl mRNA、Cry-1 mRNA、Clock mRNA表达显著性上调(P<0.01)。结论 6月龄APP/PS1双转基因痴呆小鼠的自主活动丧失正常小鼠昼少夜多的节律特征,表现为自主活动增多。生慧汤和褪黑素能有效的减少自主活动,又以减少白昼自主活动为主,使其恢复昼伏夜出的活动节律,其机制与上调一系列下丘脑生物钟基因有关。
Objective To observe the effect of Shenghui Decoction on the circadian rhythm of APP / PS1 double transgenic dementia mice and to explore its mechanism. Methods Forty five-month-old APP / PS1 double transgenic dementia mice were randomly divided into model control group, melatonin group and Shenghui Tang high and low dose groups, 10 same genetic background C57BL / 6J mice as blank control Group, intragastric administration for 1 month. The autonomic activity video analysis system was used to observe the autonomic activity time of mice at 8 time points within 24 hours and compare the sum of autonomic activity time (t_ (all)) at 8 time points in each group. Autonomous activity time (T_L) and the time of self-activity (t_D) at 4 time points in dark period (t_L), and the temporal biological characteristics were analyzed by cosineor Matlab software. The mRNAs of a series of circadian clock genes in hypothalamus were detected by Real Time-PCR expression. Results Compared with the blank group, the t_ (all), t_L and t_D of the model group increased significantly (P <0.01). Compared with the model group, the t_ (all) t_L were significantly shorter (P <0.05, P <0.01), while t_D no significant difference (P> 0.05). In the blank group, melatonin group and Shenghui Decoction high and low dose groups, the autonomic activity time can fit the cosine curve (P <0.05), showing a typical circadian rhythm, and the fitting cosine curve amplitude order is: Sheng Hui Tang high dose group> blank group> Sheng Hui Tang low dose group> melatonin group. Compared with the blank group, the expression of Perl mRNA, Cry-1 mRNA, Clock mRNA, Bmall mRNA and Rev- (P <0.01). Compared with the model group, the expressions of Perl mRNA, Cry-1 mRNA, ClockmRNA, Bmall mRNA and Rev-erba mRNA in melatonin group were significantly increased (P <0.01) (P <0.01). The expression of Perl mRNA, Cry-1 mRNA and Clock mRNA in Sheng Hui Tang low dose group was significantly increased (P <0.01). Conclusion Autonomic activities of 6-month-old APP / PS1 double transgenic dementia mice lose their circadian rhythm of day-night and night-less in normal mice, showing an increase of autonomic activity. Sheng Hui Tang and melatonin can effectively reduce autonomic activity, but also to reduce the autonomic activity-based, to restore the nocturnal activity rhythm, the mechanism and up-regulation of a series of genes related to the hypothalamus circadian clock.