The Effect Of Peaoniflorin On Biological Rhythm Of Depression Modal Rat And The Research Of Its Mechanism

Objectives:Explore the effect of paeoniflorin on circadian rhythm in depression model rat and the expression of bioclock gene Clock and Bmall in rat hippocampus zone.Moreover,investigate paeoniflorin's antidepression effect and its mechanism from improving biological rhythm,so as to provide a therapy insight.Methods:3 or 4 months old rats were randomly divided into five groups:the control group,the model group,the melatonin group,the low-dose paeoniflorin group and the high-dose paeoniflorin group.The control group were adapt in normal environment.And the other groups were conducted the various unpredictable stimulus within 28 days.From the 8th day,the model group rats were ereated normal saline.The melatonin group rats were ereated agomelatine 40 mg·kg-1·d-1.The low-dose paeoniflorin group rats were ereated paeoniflorin 5 mg·kg-1·d-1 and the high-dose paeoniflorin group rats were ereated paeoniflorin 15 mg·kg-1·d-1.At the 28th day,rats were tested respectively for their behaviors to detect depression changes.At the 28th,the rats' body temperatures were monitored and the changes were recorded in 24h.PCR was employed to compare the circadian rhythm of clock gene in hippocampus zone among these groups.Meanwhile,the expression of bioclock mRNA and protein in hippocampus zone was analyzed through the methods of PCR,western blotting and Immunohistochemistry.Results:1.The behavior test showed that the model ranked the top of the weight,horizontal motion,vertical movement and the immobility time in forced swimming test among these groups(P<0.05).The rat temperature timing cosin fitting curve in 24h released the model group appeared obviousely higher than the control group on median,amplitude and peak position(P<0.05),but appeared the lower valley position(P<0.05).Contrast with the model group about median,amplitude and peak position,the control group,the agomelation group and the high-dose group were lower obviousely,but the low-dose group had no clear difference from the model(P>0.05).2.Rats were observed for the expression of clock&bmall gene through cosinor waves of the circadian rhythm.The bioclock gene Bmall indicates that the model group were transcribed higher than the control in the aspect of median,amplitude,peak,valley position,and the melatonin group and the high-dose group were apparently lower than the model(P<0.05).The low-dose group were obviously lower than the model on the median,amplitude,peak position(P<0.05),but the low-dose group appeared had no obviously difference on valley position(P>0.05).In the wave of Clock gene mRNA pression,in the aspect of median,amplitude,peak,valley position,the model appeared more higher than the control,and the three given drug group had the lower position than the model's.3.Compared with the mRNA and(P<0.05)protein expression of the gene clock&bmall of rats at the same time,the model group was higher than the normal group(p<0.05).Contrasted with the model,the agomelatin and low/high-dose paeoniflorin showed the less bioclock gene clock&bmall in mRNA expressing.The melatonin,the high-dose paeoniflorin showed the less clock protein than model group(p<0.05),but the low-dose group showed less expressing in Clock protein(P<0.05)and had no obviously difference in Bmall protein(P>0.05).Conclusion:1.Paeoniflorin can improve the symptoms in depression rats,and change the circadian rhythm of temperature.2.In rat depression model,the circadian rhythm is changed in bioclock gene mRNA expressing in hippocampus zone.The circadian rhythm of biaoclock gene in depression model rat can be improved by paeoniflorin.3.Paeoniflorin might play a role of antidepression effect by the expression of bioclock gene in hippocampus zone.