The Effects Of YangShenDingZhi Granule On CAMP-PKA-CREB-BDNF Signaling Pathway And Inflammatory Factors In Insomnia Rats

Objective: To establish an insomnia rat model,observe and compare the behavioral changes among rats and the differences of related protein expression in hippocampus and striatum,and study the effects of Yang Shen Ding Zhi granule on the behavioral behavior of rats with insomnia,and the effects of Yang Shen Ding Zhi granule on c AMP-PKA-CREB-BDNF signaling pathway and inflammatory factors in rats with insomnia.To investigate the effect mechanism of Yang Shen Ding Zhi granule on c AMP-PKA-CREB-BDNF signaling pathway and inflammatory factor TNF-α in rats with insomnia,the expression of related proteins in this signaling pathway was changed.Methods: Forty-eight SPF male SD rats were randomly divided into blank control group(n = 8)and model group(n = 40)after adaptive feeding for one week and the insomnia rat model was established by PCPA.After successful modeling,the modeling group was randomly divided into 5 groups,including model group,diazepam group,Yang Shen Ding Zhi granule low-dose group,Yang Shen Ding Zhi granule medium-dose group,and Yang Shen Ding Zhi granule high-dose group,with 8 mice in each group.The blank control group and model group were given normal saline,and the others were given corresponding drugs,once a day,for consecutive 7 days.The sleep quality and behavior of rats were evaluated by pentobarbital sodium hypnosis test and open field test.The content of TNF-α in serum and c AMP in hippocampus and striatum were detected by Elisa.The contents of PKA and BDNF in the hippocampus and striatum were detected by RT-PCR.Western blot was used to detect the content of p-CREB in the hippocampus and striatum.Results: Compared with the blank control group,the bodyweight of the model group was significantly decreased(P<0.001),sleep latency and sleep duration of rats in the pentobarbital hypnosis experiment were significantly prolonged(P<0.01),and the total distance of field was significantly increased(P<0.001).Serum TNF-α content was significantly increased(P<0.001),c AMP content in hippocampus and striatum was significantly decreased(P<0.05,P<0.01),PKA content in the hippocampus was significantly decreased(P<0.05),p-CREB content in the striatum was significantly decreased(P<0.01),and BDNF expression showed a decreasing trend.Compared with the model group,the bodyweight of the Yang Shen Ding Zhi Granule group and diazepam group was significantly increased,sleep latency and sleep duration were significantly shortened,a total distance of field was significantly reduced,serum TNF-α expression was significantly decreased,and the expressions of other proteins showed an increasing trend.The expressions of c AMP and PKA in the hippocampus were significantly increased in the Yang Shen Ding Zhi granules high-dose group(P<0.05),and the expressions of c AMP and p-CREB in the striatum were significantly increased in Yang Shen Ding Zhi granules low-dose group(P<0.01,P<0.05).Meanwhile,the expressions of these two indexes were also significantly increased in the Yang Shen Ding Zhi granules medium-dose group(P<0.05).Conclusion: Yang Shen Ding Zhi granules can improve sleep quality and anxiety-like behavior of insomnia rats by up-regulating c AMP-PKA-CREB-BDNF signal pathway in hippocampus and striatum and down-regulating inflammatory factor TNF-α.