| Objective:To investigate the effect of melatonin receptor agonist Agomelatine and antagonist Luzindole on the progression of 6-OHDA-induced Parkinson’s model rats.Methods:1.A single injection of 6-hydroxydopamine to the right medial forebrain bundle(MFB)to establish a rat model of Parkinson’s Disease(PD),the rats were divided into 6 groups: Cont+NS,Cont+AG,Cont+LU,PD+NS,PD+AG,PD+LU.The corresponding drugs were intraperitoneally injected for 30 minutes after operation,respectively,for 2W and 4W(Cont: control group;PD: Parkinson model group;NS: normal saline 9 mg/kg;AG: agomelatine injection 16 mg/kg;LU: Luzindole injection 10mg/kg).2.Apomorphine(APO)induced rotation test was performed every 1W intraperitoneally,and the behavioral changes of rats were observed.3.ELISA was used to detect serum melatonin(MLT)levels in rats.4.Immunohistochemical staining was used to observe the survival of dopaminergic neurons in the substantia nigra pars compacta(SNc).5.Western blot was used to detect the expression of tyrosine hydroxylase(TH)and melatonin receptor subtype 1A/B(MEL-1A/B)protein in the unlesion side and lesion side of rat striatum.6.Analysis of the correlation between MLT levels and APO,and the level of MLT and the number of TH positive cells on the SNc lesion side.Result:1.After administration of melatonin receptor agonists and antagonists,the behavioral results of rats showed that the number of rotations of the rats in 1W-4W PD group after modeling was significantly higher than that of the corresponding control group(p<0.01),and the number of rotations in the PD+NS group was 4W>3W>2W(p<0.05),at 3W and 4W,the number of rotations in the PD+AG group and the PD+LU group was significantly lower than that in the PD+NS group(p<0.05).2.After administration of melatonin receptor agonists and antagonists,(1)The results of serum melatonin concentration showed that after administration of 2W,PD+NS group was higher than Cont+NS group and PD+LU group(p<0.05);after administration of 4W,Cont+AG group and The PD+NS group was higher than the Cont+NS group,the PD+NS group was higher than the PD+LU group(p<0.05),and the 4W melatonin was in the Cont+AG group,PD+NS group,and PD+AG group.The concentrations were all above 2W(p<0.05).(2)Western blot results showed that the expression of MEL-1A/B protein in rat striatum was not statistically significant after 2W administration;after administration of 4W,Cont+AG group and PD+NS The expression of MEL-1A/B protein in the striatum of the unlesion side striatum was higher than that in the Cont+NS group.The lesion side of the Cont+AG group was higher than that of the Cont+NS group(p<0.01).3.After administration of melatonin receptor agonists and antagonists,(1)Immunohistochemical staining showed that after administration of 2W and 4W,the number of TH positive cells in the dense part of the substantia nigra of the PD group was significantly less than that of the Cont group and the PD group.On the side(p<0.001),the lesion side of the PD+AG group and the PD+LU group were more than the lesion side of the PD+NS group(p<0.01).(2)After 2W and 4W,the expression of TH protein in the striatum of the injured group was lower than that of the contralateral side of the Cont group and the unlesion side of the PD group(p<0.05).After 4W administration,the unlesion side expression of TH protein in the striatum of PD+NS group was lower than that in Cont+NS group(p<0.01),and the unlesion side of PD+AG group was lower than that in Cont+AG group(p<0.05),The lesion side of the PD+AG group and the PD+LU group were higher than those of the PD+NS group(p<0.01).4.Correlation analysis showed that:(1)After administration of 2W and 4W,serum MLT levels were positively correlated with APO-induced rotational behavior,and when 4W was |r|(r=0.8987)(p<0.0001)was greater than 2W |r|(r=0.5985)(p<0.05);rats in the control group and PD group after the administration of the agonist 2W |r|(r=0.9453)(p<0.0001)were significantly larger than the rats in the control group and the PD group |r|(r = 0.5985)(p < 0.05).(2)After administration of 2W and 4W,serum MLT levels were negatively correlated with the number of TH positive cells on the SNc destruction side,and |r|(r=-0.8897)at 4W(p<0.001)was greater than 2W |r|(r=-0.6791)(p<0.05);rats in the control group and the PD group after the administration of the agonist 2W |r|(r=-0.9443)(p<0.0001)were significantly larger than the rats in the control group and the PD group |r|(r =-0.6791)(p < 0.05).Conclusion:1.Melatonin receptor agonist AG can improve the motor symptoms of PD model rats,has a certain protective effect on dopaminergic neurons in the substantia nigra pars compacta,and has a good stimulating effect on melatonin receptors to increased melatonin levels.2.The melatonin receptor antagonist LU may have an indirect protective effect on dopamine neurons,and has a good antagonistic effect on melatonin receptors to lower melatonin levels. |
