Effect And Mechanism Of Paeoniflorin On Improvement Of Depressive And Anxious Behavior Induced By Bayk8644 In Rats

Purpose: The rats were induced by L type calcium channel agonist Bayk8644,with paeoniflorin intervention,the behavior changes of rats were detected by open field test and elevated plus maze test.the expression of key protein expression and neurotransmitter release of L calcium channel were detected by Western Blot and microdialysis,to investigate the pharmacological mechanism of paeoniflorin in treating mental disorders through L type calcium channels.Method:1.The rats were divided into Bayk8644 group,control group,high dose of paeoniflorin group(200mg/kg/d),paeoniflorin dose group(100mg/kg/d),paeoniflorin low dose group(50mg/kg/d)and nimodipine group(1mg/kg/d)by the scores of sucrose preference and open field test.After 7 days of intragastric administration,the rats were peritoneal injection with Bayk8644,the behavioral data of rats were collected by open field test and elevated plus maze test.The hippocampal brain area was separated,and the expression level of CaMKⅡ,BDNF and pho-CaMKⅡ in each group was detected by Western Blot.2.The rats were divided into Bayk8644 group,high dose of paeoniflorin group and nimodipine group by the scores of sucrose preference and open field test.After sixth days of intragastric administration,intracerebral stereotatic of rats hippocampal(AP-5.8 mm,ML-4.6 mm,DV-5.0 mm),After seventh days of intragastric administration,microdialysis collection of extracellular fluid,flow rate of 1.5 μL/min,collection of samples per 20 min,collects a total of 5 h.HPLC-ECD method was used to detect the changes of DA,5-HT,GABA and Glu in the extracellular fluid of the hippocampus of rats.Results:1 Macroscopic behavior results showed that,after administration,compared with the control group,the total distance,the center distance,the center zone entries and the number of upright of OFT and the total distance,the average velocity,the percentage of times,the percentage of time of elevated plus maze test of the Bayk8644 group were significantly decreased(P<0.05 or P<0.01).Compared with the Bayk8644 group,the total distance,the center distance,the center zone entries and the number of upright of OFT and the total distance,the average velocity,the percentage of times,the percentage of time of elevated plus maze test were significantly increased(P<0.05 or P<0.01)in high dose of paeoniflorin group.2 Wstern blot results showed that: compared with the control group rats,Bayk8644 group CaMKⅡ and pho-CaMKⅡ protein expression was significantly increased(P<0.05 or P<0.01),the expression of BDNF protein was significantly decreased(P<0.05);compared with the Bayk8644 group,paeoniflorin in high-dose group rats CaMKⅡ and pho-CaMKⅡ protein expression significantly decreased(P<0.05 or P<0.01),BDNF protein expression was significantly increased(P<0.05).3 Microdialysis results showed that,the content of GABA and 5-HT in the group of nimodipine and paeoniflorin high dose were all higher than in the group of Bayk8644,the content of Glu was lower than in the group of Bayk8644,and the content of DA in the group of paeoniflorin high dose was higher than than in the group of Bayk8644 and nimodipine,and the content of DA in the group of nimodipine and Bayk8644 were no different.The results showed that,compared with the Bayk8644 group,after injection of Bayk8644 20 min,140 min and 260 min,the content of Glu in the high dose group of paeoniflorin decreased significantly(P<0.01 or P<0.05).After 60 min and 140 min,the content of 5-HT in the nimodipine group and the high dose group of paeoniflorin increased significantly(P<0.05).After 140 min,the contents of the nimodipine group were contained.After 180 min and 220 min,the content of GABA in nimodipine group and paeoniflorin high dose group increased significantly(P<0.01 or P<0.05),After 100 min,140 min and 180 min,the content of DA in high dose group of paeoniflorin increased significantly(P<0.05)and then declined.Conclusions: Paeoniflorin may play a pharmacological role in the treatment of mental diseases by affecting the expression of L-type calcium channel related proteins and the release of neurotransmitters.The CaMKⅡ /BDNF pathway mediated by L channel is the target of its pharmacological action.