Effects of Jiaotai Pill self-microemulsion on neurotransmitters and intestinal flora in insomnia rats
Objective To observe the effects of Jiaotai Pill self-microemulsion(JPSM)on the intestinal flora and neuro-transmitters including 5-hydroxytryptamine(5-HT),dopamine(DA)and noradrenaline(NE)etc in the hypothalamus of in-somnia rats,and evaluate the intervention effect of JPSM on insomnia and the mechanism.Methods Dl-4-chlorophenylalanine was intraperitoneally injected to establish the insomnia rat models.JPSM,unilateral coptis self-mi-croemulsion and cinnamon self-microemulsion were given to the rat models by gavage,with diazepam and jujube seed de-coction as the positive control drugs respectively.The ethological characteristics of rats each group were observed.The activity of 5-HT,NE and DA in hypothalamus were measured.The changes of intestinal flora was determined using high-throughput sequencing.Results The time of autonomous activity and times of forelimb off the ground in the model group were higher than those in the normal control group(t=8.935 4,10.568 2;P=0.005 2,0.004 7).After treatment,the values in each group decreased compared with the model group.In the model group,the content of 5-HT in the hypothalamus signi-ficantly decreased,while those of NE and DA significantly increased(t=8.472 9,15.497 3,21.885 7;P=0.006 8,0.005 7,0.007 2).Compared with the model group,the contents of 5-HT in diazepam group,Suanzaoren Decoction group,unilater-al Coptis group,JPSM high-and medium-dose groups increased significantly(t=40.547 7,28.673 2,15.635 4,17.498 0,36.498 6;P=0.005 4,0.003 9,0.006 3,0.003 8,0.004 1),while those of NE and DA decreased significantly(t=12.462 2,8.498 6,24.558 6,18.876 0,7.445 8;P=0.004 9,0.006 7,0.005 4,0.007 5,0.024 1 and t=24.483 7,12.811 2,24.446 4,32.454 1,16.839 0;P=0.000 1,0.003 4,0.000 1,0.000 1,0.000 7);there was no significant difference in the contents of 5-HT,NE and DA in the low-dose JPSM group compared with model group(t=16.854 3,24.385 5,45.186 5;P=0.086 4,0.105 7,0.176 4).Alpha diversity analysis showed that the average indexes of Observed species,Chaol and Shannon in the model group significantly reduced.Compared with the model group,the abundance and diversity of bacterial flora in the other administration groups recovered.Beta diversity analysis showed that,compared with the normal control group,the species structure of intestinal flora in the model group was significantly different,and the structures of intestinal flora in the other administration groups changed.Conclusion JPSM can increase the contents of 5-HT and DA,and decrease that of NE in hypothalamus of rats with insomnia.The decrease of NE can increase the intestinal flora abundance of insomnia rats,and there is a correlation between the two changes.Jiaotai Pill may play a role in treating insomnia by affecting the intest-inal flora abundance of insomnia rats and regulating the levels of neurotransmitters.
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