Objective

2

To explore the possible mechanism of

Geng Xin Decoction

（更欣汤， GXD） in treating perimenopausal insomnia.

Methods

2

Fifty-two out of 60 SD female rats with regular estrous cycle were selected and randomly divided intoblank group （n=13） and modeling group （n=39）. The rats in the modeling group were given tripterygium glycosides by gavage and intraperitoneal injection of p-chlorophenylalanine （PCPA） suspension to establish the perimenopausal insomnia rat model. Twenty-six successfully modeled rats were randomly divided into a model group and GXD group with 13 rats in each group. Rats in the GXD group were given 1.8 g/（kg·d） of

Geng Xin Decoction

granules by gavage every day， while those in the blank group and model group were given 10 ml/（kg·d） of normal saline by gavage every day， all for 14 days. The general behavioral changes of rats were observed. Pentobarbital sodium synergistic experiment was applied to detect the sleep status of the rats including sleep latency and sleep duration. Western blotting was used to detect the protein expression of biological clock gene CLOCK， BMAL1， Per1， and Per2 in the hypothalamus， and RT-qPCR method was used to detect the mRNA expression of CLOCK， BMAL1， Per1， and Per2.

Results

2

The results of pentobarbital sodium synergistic experiment showed that the sleep duration was prolonged in the model group and GXD group than in the blank group （

P

＜0.05）， while no significant difference was found among the three groups in the sleep latency （

P

＞0.05）. Compared to those in the blank group， the rats in the model group were in poor mental state and were active both in the daytime and at night in the early stage， showing an arousal state with decreased food and water intake， hair erection with light yellow， dry， and easy to fall off hair； the stool was yellow-green， soft or thin； the protein expression level of CLOCK and BMAL1 in hypothalamus increased， while the protein expression level of Per1 and Per2 decreased （

P

＜0.05 or

P

＜0.01）. Compared to those in the model group， the mental state of the rats in GXD group was significantly improved， and the daytime activities of the rats decreased， with slightly yellow but shiny hair， and formed stool； the protein expression level of Per2 increased， while that of CLOCK， BMAL1 and Per1 protein was not statistically significant （

P

＞0.05）. There was no significant difference in the relative mRNA expression of CLOCK， BMAL1， Per1 and Per2 in the hypothalamus among the groups （

P

＞0.05）.

Conclusion

2

The mechanism of GXD in improving the sleep state of perimenopausal insomnia rats may be related to the up-regulation of protein expression of the biological clock gene Per2 in the hypothalamus.