The Neuroprotective Effects Of DL-3-n-butylphthalide (L-NBP) In Arkinson's Disease In Mice Induced By Intraperitoneal Injection Of LPS

Objective:The mice model of Parkinson's disease(PD),induced in C57BL/6 mice,were established by intraperitoneal injection of lipopolysaccharide.The purpose of this study was exploring the neuroprotective effects and mechanisms of L-BNP in the mice model of PD.Methods:60 male C57BL/6 mice were randomly divided into 3 groups: normal control group;LPS group and LPS+NBP group.The mice model of Parkinson's disease was made by a single intraperitoneal injection of LPS(5 mg/kg).LPS+NBP group,wherein mice received NBP(120 mg/kg,solube in 1 ml vegetable oil)orally for 21 days(Days1–21)and were injected with LPS(similar to the LPS group);and control group,wherein mice were treated with corresponding normal saline.1.The rotarod test and the open-field test were performed on Days 30,Days 90,Days150 and Days 210.In order to observe the amount of tyrosine hydroxylase(TH),IBA-1 positive cells(activated microglia)and IL-1?,in the substantia nigra pars compacta(SNpc),the mice were sacrificed after the behavioral observation.2.The rotarod test and the open-field test were performed on Days 210.In order to observe the expression of tyrosine hydroxylase(TH),IBA-1,IL-1? and CHOP in the substantia nigra pars compacta(SNpc),the mice were sacrificed after the behavioral observation.At the same time,the level of P-JNK,P-P38 and P-ERK in the substantia nigra pars compacta was detected through Western blot method.Results:1.A single intraperitoneal injection of LPS can induce behavioral disorder in C57BL/6 mice: Compared with the control group,the exercise capacity of LPS group mice did not show significant changes on the thirtieth day(P>0.01),but from the ninetieth day,the LPS group mice showed a significant decrease in exercise capacity(P<0.01),the difference was statistically significant,and gradually showed tremors,erecting hair and other symptoms of PD.2.A single intraperitoneal injection of LPS can induce long-term inflammatory response in C57BL/6 mice: Compared with the control group,the number of IBA-1,TNF-and IL-1 positive cells of LPS group mice increased significantly(P<0.01),the difference was statistically significant.3.A single intraperitoneal injection of LPS can induce the loss of DA neurons in substantia nigra in C57BL/6 mice: Compared with the control group,the TH positive neurons in the substantia nigra of LPS group mice decreased,cell dyeing was lighter,the number of cells decreased significantly(P<0.01),the difference was statistically significan.4.NBP can alleviate the behavioral disorder in LPS group mice: Compared with the model group,the mice in the treatment group showed strong motor ability(P<0.01).5.NBP can alleviate the damage of dopaminergic neurons in Parkinson's disease model mice: Compared with the model group,TH positive cells of The treatment group mice tend to be normal,the number of neurons bluge increased,the number of cells increased significantly(P<0.01).6.NBP can alleviate inflammatory response in the brain in Parkinson's disease model mice: Compared with the model group,the number of IBA-1 and IL-1?positive cells of LPS+NBP group mice decreased significantly.7.NBP can affect the activation of MAPK pathway in Parkinson's disease model mice: Compared with the control group,the expression level increased significantly of P-JNK ?P-P38 of the substantia nigra area in the model group;Compared with the model group,the expression level decreased significantly of P-JNK ?P-P38 of the substantia nigra area in the treatment group;the level of P-ERK in the three groups of mice was not statistically significant.8.NBP can improve the stress of endoplasmic reticulum in substantia nigra region of Parkinson's disease model mice: Compared with the control group,the expression level significantly increased of CHOP of the substantia nigra area in model mice(P<0.01),the level of CHOP of the substantia nigra area in model mice was not statistically significant.Conclusion:1.A single intraperitoneal injection of LPS could successfully induce a mouse model of chronic Parkinson's disease.The pathogenesis may be related to long-term persistent inflammatory response in the brain.2.NBP has neuroprotective effects on DL-3-n-butylphthalide(L-NBP)in Parkinson's disease in mice induced by intraperitoneal injection of LPS.The protective mechanism may be related to the alleviation of chronic inflammatory response in the brain,the reduction of activation of MAPK pathway and the improvement of the stress of endoplasmic reticulum.