Pathology Of Liver Catharsis Is Too Much And Pharmacodynamics Of Descending Adverse Qi-Study On The Main Pathological Changes Of Pmdd Liver Qi Inverse Rats And The Main Pharmacodynamic Mechanism Of Paeonol Drop Pill

Purpose:Guided by the theory of liver viscera in traditional Chinese medicine,study the main pathological changes of Liver-qi inversion syndrome of PMDD and PMDD and the pharmacodynamics of paeonol dropping pills in animal models.Methods:?1?Carding the source of liver catharsis is too much and it's pathology,sort out the understanding of Liver-qi inversion syndrome of PMDD in traditional Chinese medicine by bibliometric method.?2?Screening the best optimum anti-anxiety effect of paeonol drop pill by the tri-model of anxiety in mice?OFT?EPM?LDB?and the social interaction model.?3?The best dosage equivalent conversion was screened out from the mice model.One-way analysis of variance was used for comparison between groups?Bonferroni's multiple comparisons test?,One-tailed unpaired t-test was used for comparison between the two groups.Paeonol dropping pills were used to intervene to explore the main pharmacodynamics and mechanism on PWD-PMDD and PMDD rats with liver-qi inversion syndrome.Results:?1?At the screening experiment of optimum dosage of paeonol dropping pills for anti-anxiety,in the open field experiment after 3 day of administration in center distances?center time and rearings,paeonol drop pills 17.5mg/kg,70mg/kg increased significantly compared with diazepam group?p<0.05,p<0.05;p<0.05,p<0.05;p<0.01,p<0.05?,while paeonol drop pills 35mg/kg decreased significantly compared with control group?p<0.05?.Compared with the control group,the residence time in the central area and the number of rearings of diazepam group decreased significantly?p<0.05,p<0.05?after 7days of administration.In the elevated plus maze test of administration for 3 days,paeonol drop pills 17.5mg/kg was significantly increased compared with the control in the OT%results?p<0.05?,paeonol drop pills 35mg/kg was significantly decreased compared with the control and diazepam group?p<0.05,p<0.05;p<0.01,p<0.05?in the OE%and OT%results.,paeonol drop pills 17.5mg/kg was significantly increased compared with the control group?p<0.05?in the EPM OE%test of administration for 7 day.In the LDB results of 3 days administration,paeonol drop pills 17.5mg/kg was increased significantly in the light area entries compared with the control group?p<0.05?.In the movement distance?the entry time in the light area?and the number of entry in the light area of 7 days administration,paeonol drop pills 17.5mg/kg was significantly increased compared with the control group?p<0.05,p<0.05,p<0.05?,and 35mg/kg was significantly increased compared with the control group in the distance of light area?p<0.05?.In the social interaction model results of 3 days of administration,paeonol drop pills 35mg/kg showed a significant decrease in the first phase of social interaction compared with the diazepam and control group?p<0.005,p<0.005?.In the results of 7 days of SIT administration,paeonol drop pills 17.5mg/kg and 35mg/kg were significantly increased compared with the control and diazepam group?p<0.05,p<0.005;p<0.05,p<0.01?.?2?In the PMDD rat model,compared with the control group in the OFT test,the residence time in the central area and the number of rearings in the model group was decreased significantly?p<0.05,p<0.05?,and paeonol 24.23mg/kg decreased significantly?p<0.05?in the number of rearings compared with the model group.In EPM test,compared with the control group,the model group was decreased significantly in OE%and OT%?p<0.01,p<0.01?,paeonol drop pills 6.05mg/kg increased significantly in OT%and OE%?p<0.01,p<0.01?.In the LDB test,Compared with the model group,24.23mg/kg in the light area movements and entries was decreased significantly?p<0.01,p<0.005?,6.05mg/kg was decreased significantly in the light area distance?the number of entries and the time in the light area?p<0.05,p<0.05,p<0.05?.In ELISA test,the hippocampus E₂ content in model group was significantly lower than that in control group?p<0.05?.Compared with model group hippocampus,6.05 mg/kg increased significantly in P,ALLO and E₂ test?p<0.005,p<0.01,p<0.001?;12.11mg/kg was increased significantly in ALLO and E₂ hippocampus test?p<0.01,p<0.01?;24.23mg/kg was increased significantly in E₂ hippocampus test?p<0.005?.In the UHPLC-MS/MS test,GABA in hippocampus was significantly lower in model group than in control group?p<0.05?;6.05mg/kg was significantly higher in GABA and NE than in model group?p<0.05,p<0.05?;12.11mg/kg was significantly higher in NE?p<0.05?.?3?In the rat model of PMDD with liver-qi inversion syndrome,RIT test showed that the aggressive score of model group was significantly higher than that of control group before and after administration?p<0.001,p<0.001?;Before administration,there was no significant difference between paeonol group and stress group?p>0.05?,but after administration,the aggressive score of paeonol group was decreased significantly?p<0.001?.In the OFT test,compared with the control group,the movement distance and residence time of the central area in the stres group was decreased significantly before and after administration?p<0.01,p<0.01;p<0.05,p<0.01?.In EPM tests,the stress group compared with the control group before administration of OE%?OE%and after administration of OT%were decreased significantly?p<0.05,p<0.05,p<0.005?.Compared with stress group,paeonol drop pills 12.11mg/kg was increased significantly after administration in OE%and OT%?p<0.05,p<0.005?.In ELISA test,the ALLO content in serum of stress group was significantly lower than that of control group before and after administration?p<0.01,p<0.05?.In P and ALLO test after administration compared with stress group,12.11mg/kg was increased significantly,and 24.23mg/kg was increased significantly in ALLO test?p<0.05?.Compared with the stress group,12.11mg/kg and6.05mg/kg in the hippocampal brain was increased significantly in P and E₂ test?p<0.05,p<0.01,p<0.05,p<0.005?,and 24.23mg/kg in E₂ test was increased significantly?p<0.01?.In the UHPLC-MS/MS test,NE in hippocampus was significantly lower in the model group than in the control group?p<0.05?,and 12.11mg/kg in paeonol group was significantly higher than that in the model group?p<0.05?.In RT-PCR test,GABA_AR?₄mRNA in stress group was significantly higher than that in control group?p<0.01?.Conclusion:?1?Obtion results by bibliometric method the liver-qi inversion syndrome of PMDD is related to the abnormality of liver catharsis,treatment of PMDD Liver-Qi Inverse syndrome should use the method of calming Liver and reducing outrise.?2?Paeonol dropping pills 17.5mg/kg showed the best anti-anxiety effect in mice with anxiety triple model and social interaction model.?3?Paeonol drop pills 6.05mg/kg can correct anxiety-like emotional behavior in the rat model of PMDD;Paeonol dropping pills12.11mg/kg can correct the behavior of a rat model of irritable mood PMDD liver-qi invasion.In the PMDD liver-qi syndrome model,the decrease of serum ALLO in the non-reccepting period caused NE decrease and GABA_AR?₄ mRNA up-regulation in the hippocampus,results in RIT?OFT?EPM shows irritability;Paeonol drop pills may increase the content of NE in the serum and the level of NE in the hippocampus.Altering the GABA_AR receptor improves the irritability and irritation behavior of the rat model of PMDD liver-qi reversal.