Effect Of 5-BDBD On Expression Of NLRP3 And Caspase-1 In Parkinson’s Disease Rat Model

Objective: To investigate the effect of P2X4 receptor antagonist 5-BDBD on the expression of NLRP3 and caspase-1 in Parkinson’s disease(PD)rat model induced by 6-OHDA.Methods: Wistar male rats were divided into 4 groups(n=30):(1)control group: one week after normal saline pretreatment,0.02% ascorbic acid was stereotactic injected into the left substantia nigra;(2)6-OHDA group: one week after normal saline pretreatment,6-OHDA was stereotactic injected into the left substantia nigra;(3)5-BDBD group: one week after 5-BDBD pretreatment,0.02% ascorbic acid was stereotactic injected into the left substantia nigra;(4)5-BDBD+6-OHDA group: one week after 5-BDBD pretreatment,6-OHDA was stereotactic injected into the left substantia nigra.Four weeks after the completion of modeling,the rats were killed and the brain tissues were got out.TH-positive neurons in PD rats substantia nigra were detected by immunohistofluorescence stain.The relative mRNA level of P2X4 R,NLRP3 and caspase-1 was measured by RT-PCR.The relative protein level of P2X4 R,NLRP3 and caspase-1 was measured by Western-blot.Results: Compared with the control group and 5-BDBD group,the TH-positive neurons were decreased in 6-OHDA group and 5-BDBD+6-OHDA group(F=162.7,P<0.01);the mRNA level of P2X4 R,NLRP3 and caspase-1were increased in 6-OHDA group and 5-BDBD+6-OHDA group(F=59.13,F=635.9,F=538.0;P<0.01);the protein level of P2X4 R,NLRP3 and caspase-1were increased in 6-OHDA group and 5-BDBD+6-OHDA group(F=269.3,F=120.3,F=141.1;P<0.01).Compared with 6-OHDA group,the TH-positive neurons were increased in 5-BDBD+6-OHDA group(F=162.7,P<0.01);the mRNA level of P2X4 R,NLRP3 and caspase-1 were decreased in5-BDBD+6-OHDA group(F=59.13,F=635.9,F=538.0;P<0.01);the protein level of P2X4 R,NLRP3 and caspase-1 were decreased in 5-BDBD+6-OHDA group(F=269.3,F=120.3,F=141.1;P<0.01).Conclusion: The results suggested that inhibiting the P2X4 R could inhibit the inflammatory reaction and the degeneration of dopaminergic neurons of PD rat model,and inhibit the expression of NLRP3 and caspase-1 induced by 6-OHDA,which had a potential neuroprotective effect.