Changes Of Magnesium Ion Concentration And Magnesium Ion Transporter In Serum And Brain Tissue In 6-OHDA-induced Parkinson’s Rats

Background:Parkinson’s disease（Parkinson’s disease,PD）is the second largest degenerative disease of the central nervous system.The main pathological changes are degeneration and death of dopaminergic neurons in the dense part of the midbrain substantia nigra.The main clinical manifestations are bradykinesia,muscular rigidity,resting tremor,postural instability and non-motor symptoms,but the exact pathogenesis has not been fully elucidated.At present,the existing treatments for PD can only be used to alleviate gradually increasing movement disorders,and still cannot cure it.Objective:To study the changes of magnesium ion concentration in serum and brain tissue and magnesium ion transporters SLC41A1 and Mag T1 in the progression of6-OHDA-induced Parkinson’s disease rat model,and the relationship between them.Methods:1.Single-point injection of 6-hydroxydopamine（6-hydroxydopamine）into the right medial forebrain bundle（Medial forebrain bundle,MFB）to establish a PD rat model,divide the rats into 4 groups:control group（Cont）and control magnesium supplement group（Cont+Mg）,Parkinson’s model group（PD）,Parkinson’s model magnesium supplement group（PD+Mg）.The model was injected intraperitoneally for the first time 30 minutes after modelling,NS was injected into the control and PD group,MgSO₄was injected into the Cont+Mg group and PD+Mg group,and intraperitoneal injections were continued for 2 weeks and 4 weeks at the same time each day（NS:physiological saline 9mg/kg;Mg:MgSO₄.7H₂O,90mg/kg）.2.Apomorphine（APO）was injected intraperitoneally at 2 weeks and 4 weeks after modeling to induce the rotation experiment to observe the behavioral changes of rats.3.Immunohistochemical staining was used to observe the survival of substantia nigra pars compacta（SNc）dopaminergic neurons.4.Western blot detected the expression of magnesium ion transporters SLC41A1and Mag T1 proteins in the rat striatum health and damaged side.5.Magnesium ion kit was used to detect serum magnesium ion,substantia nigra and striatum magnesium levels in rats.Result:1.After daily intraperitoneal injection of MgSO₄for 2W and 4W,the behavioral results induced by APO showed that the number of rotations of rats in PD group and PD+Mg group was significantly higher than that in Cont group and Cont+Mg group（p<0.001）;the number of rotations of the PD+Mg group at 4W was significantly lower than that of the PD group（p<0.01）.2.After the administration of MgSO₄for 2 weeks and 4 weeks,TH（positive markers of dopamine neurons）positive cells in the dense side of the midbrain substantia nigra of PD group and PD+Mg group were significantly lower（p<0.001）compared with the Cont groups and Cont+Mg groups,and the damaged side of the PD group and PD+Mg group were also significantly lower than that of the healthy side（p<0.001）.After administration of MgSO₄for 2 weeks and 4 weeks,the TH⁺positive neurons in the PD+Mg group were significantly higher than those in the corresponding PD group（2 weeks,p<0.05;4 weeks,p<0.01）3.After the administration of MgSO₄for 2 weeks,the expression of SLC41A1protein in the healthy and damaged sides of the PD group was significantly lower than that of the Cont group.（The healthy side,p<0.05;the damaged side,p<0.01）;the expression of Mag T1 protein on the damaged side of the PD group was also lower than that of the Cont group（p<0.05）;after MgSO₄was given for 4 weeks,the expression of SLC41A1 protein on the damaged side of the PD group increased compared with the corresponding side of 2 weeks,but there was no statistical significance;the change of Mag T1 protein expression is not obvious.4.（1）After administration of MgSO₄for 1 weeks,2 weeks,and 4 weeks,the serum magnesium ion concentration in rats was not statistically significant among the groups.（2）The results of the magnesium ion concentration in the substantia nigra and striatum show that the magnesium ion concentration of each group given MgSO₄for 2weeks and 4 weeks has no statistical significance,however,the concentration of magnesium ions in the substantia nigra and striatum of 4 weeks rats was lower than that of the PD group at 2 weeks.Conclusion:1.6-OHDA can change the expression of the magnesium ion transporter SLC41A1 in PD rats;preventive supplementation of MgSO₄can help improve the motor symptoms of PD rats and upregulate the expression of SLC41A1 protein.2.The concentration of magnesium ions in serum and brain tissue did not change significantly during the progression of PD.3.During the progression of PD rats induced by 6-OHDA,the relationship between serum magnesium ion concentration and magnesium ion transporters SLC41A1 and Mag T1 was not obvious.