The Potential Biomarkers In MPTP/probenecid-induced Parkinson’s Disease Mice

Objective:This study established a Parkinson’s disease model induced by MPTP/p in mice,and explored potential biomarkers in peripheral blood plasma of Parkinson’s disease mice based on ultra high performance liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-Q/TOF-MS),so as to explore a new method to evaluate the effectiveness of PD model.At the same time,it also provides the latest theoretical basis and research direction for the early diagnosis of clinical Parkinson’s disease and the research and development of therapeutic drugs.Methods:1.The mouse Parkinson’s disease model induced by MPTP/p was established.Fifty C57BL/6J mice were randomly divided into control group and model group.Intraperitoneal injection of corresponding drugs,model group:MPTP·HCI(25 mg/kg),probenecid(100 mg/kg);Control group:0.9%NaCI.After intraperitoneal injection twice a week for 5 weeks,the behavioral changes of mice in both control and model group were detected by olfactory test and open field test,and the relative number of dopaminergic neurons in Substantia nigra of midbrain was detected by TH immunofluorescence.2.The plasma of mice in the control group and model group was extracted,and the non-targeted metabolic analysis based on UHPLC-Q/TOF-MS was used to explore the potential biomarkers of Parkinson’s disease mice.Results:1.Compared with the control group,the olfactory function(P<0.0001)and motor function of the model group(P<0.01)decreased;TH immunofluorescence test showed that the relative number of TH positive cells in substantia nigra in the model group was significantly lower than that in the control group(P<0.0001),2.The non-targeted metabonomics study based on UHPLC-Q/TOF-MS showed that the concentration of piperidic acid in plasma in the model group was significantly higher than that in the control group(P<0.01);Conclusion:This study reveals that piperidic acid in plasma may be a potential biomarker of Parkinson’s disease by constructing MPTP/p-induced Parkinson’s disease model and using non-targeted metabonomics based on UHPLC-Q/TOF-MS,which provides the latest theoretical basis and research direction for disease diagnosis and therapeutic drug development of Parkinson’s disease.