围绝经期综合征肝郁证大鼠主要时钟基因表达的昼夜节律

Circadian expression of major clock genes in rats with perimenopausal syndrome

目的:探讨围绝经期综合征(PPS)肝郁证大鼠主要时钟基因昼夜表达规律,探求PPS与昼夜节律变化之间的关联。方法:以3月龄雌性SD大鼠为空白对照组,12~13月龄PPS SD大鼠为研究对象,采用自然衰老法和慢性束缚应激法建立PPS肝郁证大鼠模型,采用Real-time PCR方法检测大鼠下丘脑主要时钟基因Clock、Bmal1、Per1、Per2、Cry1和Cry2的表达水平及节律。结果:3组大鼠Per2、Cry1和Cry2的表达量变化呈近日节律,其中PPS肝郁证组Per2和Cry2的表达振幅显著高于空白对照组和PPS组,峰/谷值分别为12.37、7.66,峰值相位均出现在20:00左右。空白对照组和PPS组的Clock、Per1表达呈近日节律,PPS肝郁证组Clock、Per1的近日节律消失。3组大鼠的Bmal1表达均不能用余弦函数拟合。结论:PPS肝郁证与主要时钟基因表达的异常之间可能存在相互促进关系。

Objective:To study the circadian expression of major clock genes in the perimenopausal syndrome(PPS)rats with liver-qi stagnation syndrome,and to explore the relationship between circadian rhythm irregularity and liver-qi stagnation syndrome in rats.Methods:Three-month-old SD female rats and 12~13-month-old PPS SD rats were used to establish rat model of PPS with liver-qi stagnation syndrome by chronic immobilization stress method.Major clock genes(Clock,Bmal1,Per1,Per2,Cry1 and Cry2)in hypothalamus were then quantitatively analyzed by Realtime PCR.Results:The expressions of Per2,Cry1 and Cry2 in the hypothalamus of all the three experimental groups displayed a circadian rhythm.The relative expressions of Per2 and Cry2 in the group of PPS with liver-qi stagnation syndrome were respectively and significantly higher than those in the control and PPS groups,with the peak phases both appeared at 20:00 and the peak/trough(P/T)value of 12.37 and 7.66,respectively.The expressions of Clock and Per1 in the control and PPS group showed a similar circadian rhythm,which disappeared in the group of PPS with liverqi stagnation syndrome.The expressions of Bmal1 in the three groups could not be simulated by the cosine function.Conclusion:There might be a correlation between liver-qi stagnation syndrome and the modification of main clock gene expression during PPS.