Effects Of Jieyu Anshen Decoction Combined With Alprazolam On GABA,Glu,TNF-αand IL-6 In Hypothalamus Of Insomnia Rat Model With Liver Depression

Objective: To investigate the effects of Jieyu Anshen Decoction combined with Alprazolam on the ratio of neurotransmitters GABA,Glu and Glu/GABA and the contents of inflammatory factors TNF-α and IL-6 in the hypothalamus of rats with liver depression and insomnia model.Methods: Fifty healthy SPF SD rats aged 6-8 weeks were selected and randomly divided into normal group and model group(model blank control group,western medicine group,Chinese medicine group and Chinese and western medicine combined group).In the model group,p-chlorophenylalanine(PCPA)was intraperitoneally injected on an fasting stomach to make the model of insomnia rats,and pentobarbital sodium was injected intraperitoneally 36 hours later to simulate hypnosis.The sleep latency time and sleep duration of the rats before and after the model and medication were observed.The behavioral index was used to observe whether the model rats were consistent with the syndrome of insomnia of liver depression type.The rats in normal group and model blank control group were gavaged with distilled water,and rats in treatment group were gavaged with alprazolam,Jieyu Anshen decoction and Jieyu Anshen decoction plus alprazolam,respectively.After 7 days of anesthesia,hypothalamus of all rats was removed,and the contents of neurotransmitters GABA and Glu and inflammatory cytokines TNF-α and IL-6 in the hypothalamus of rats were determined by enzymatic linked immunosorbent assay(ELISA).Results:(1)The righting reflex test: compared with the normal group,the sleep latency time of the model group was significantly prolonged(P<0.05);The sleep duration was significantly shortened(P<0.05).After medication:(1)Compared with the normal group,the sleep latency time of model control group was significantly prolonged(P<0.01),and the sleep duration was decreased(P<0.05);(2)compared with model blank control group,western medicine group(alprazolam)and Chinese medicine sleep latency time(resolve depression anshen decoction)group were shortened(P<0.05),sleep duration is prolonged(P<0.05),Chinese and western medicine combined group(resolve depression anshen tonga alprazolam)sleep latency time significantly shortened(P<0.01),sleep duration extended obviously(P<0.01).(2)Behavioral indicators:compared with the normal group in open field test,the median stay time of rats in model group was shortened(P<0.05),the total distance and average speed of locomotion were decreased(P<0.05),and the upright times were significantly decreased(P<0.01).Elevated cross maze test: Compared with the normal group,the percentage of The Times of entering the open arm(OE%)in the model group was decreased,but there was no statistical significance.The percentage of residence time(OT%)in the open arm of rats was decreased(P<0.05).(3)Laboratory indicators:(1)Neurotransmitters: A.Compared with the normal group,the level of Glu in the model blank control group was significantly increased(P<0.01),and the level of GABA was significantly decreased(P<0.01),while the ratio of Glu/GABA was significantly increased.B.Compared with the model blank control group,the content of GABA in Xprazolam group was significantly increased(P<0.01),and the ratio of Glu/GABA was decreased(P<0.05);The content of GABA in Jieyu Anshen Decoction was significantly increased(P<0.01).The content of Glu was significantly decreased(P<0.01),the content of GABA was significantly increased(P<0.01),and the ratio of Glu/GABA was significantly decreased(P<0.01)in the Chinese and Western medicine combination group(Jieyu Anshen Decoction and Alprazolam).C.Compared with western medicine(alprazolam)group,there were no significant changes in Glu,GABA and Glu/GABA ratio in Chinese medicine(Jieyu Anshen Decoction)group(P>0.05);The content of GABA in Chinese and Western medicine combination group(Jieyu Anshen Decoction and Alprazolam)was increased(P<0.05).D.Compared with the traditional Chinese medicine(Jieyu Anshen decoction)group,the ratio of Glu/GABA in the combination group of Chinese and Western medicine(Jieyu Anshen decoction plus prazolam)was decreased(P<0.05).(2)Inflammatory factors: A.Compared with the normal group,the contents of TNF-α and IL-6 in the model blank control group were increased(P<0.05).B.Compared with model blank control group,IL-6 content in Xprazolam group was significantly decreased(P<0.01);The contents of TNF-α and IL-6in TCM group were decreased(P<0.05);The content of TNF-α and the content of IL-6 were significantly decreased(P<0.05)in Chinese and Western medicine combination group(Jieyu Anshen Decoction and Alprazolam).C.Compared with western medicine(alprazolam)group,the content of TNF-α in Chinese medicine(Jieyu Anshen Decoction)group was decreased(P<0.05);The content of TNF-α in Chinese and Western medicine combination group(Jieyu Anshen Decoction and Alprazolam)was decreased(P<0.05),but there was no significant difference in IL-6(P>0.05).Conclusion:(1)Through intraperitoneal injection of PCPA and behavioral evaluation,the rat model of insomnia with liver depression can be successfully prepared.(2)Alprazolam,Jieyu Anshen Decoction and Chinese and Western medicine combined(Jieyu Anshen Decoction and Alprazolam)can significantly increase the sleep efficiency of model rats and improve their general state,and the combined Chinese and Western medicine group has better efficacy.(3)Chinese and western medicine combination group(Jieyu Anshen Decoction plus Alprazolam)significantly increased the content of GABA in the hypothalamus of rats,decreased the contents of Glu,Glu/GABA ratio,TNF-α and IL-6,and better improved sleep efficiency and alleviated anxiety and depression.