The Plasma Biomarkers Study Of Parkinson’s Disease In C₅₇BL/6j Mouse Model

Objective1、To observe the effect of age, drug dosage and administration period in mouse model of Parkinson’s disease, in order to analysis the most important fact of this four facts in the onset of PD, and find out an appropriate model for PD.2、Using receiver operating characteristic(ROC) curves analysis the plasma biochemical substances of mouse model in Parkinson’s disease to look for the appropriate biomarkers which are highly related to the pathological changes and do not effected by other facts. Methods1、Four facts (age, MPTP, probenecid, administration period) are set up in orthogonal design table L9(34) for grouping mice. Tyrosine hydroxylase immunohistochemistry staining(TH) positive cell counting are applied to indicate the deficit of dopaminergic neuron in substantia nigra. Swimming test and average consumption of feedstuff per week (AFP) are measured to reveal the behaviour of mice.2, Four facts (age,MPTP, probenecid administration period) are set up in orthogonal design table L9(34) for grouping mice. The plasma biochemical substances are test by high efficiency liquid chromatography(HPLC), colorimetric analysis and enzyme-linked immunosorbent assay. Tyrosine hydroxylase (TH) immunohistochemistry staining positive cell counting are applied to draw ROC. Results1、Administration period is proved the most important fact of mouse model in PD. The effect sequence of the facts is-administration period>MPTP>age>probenecid, and the most appropriate combination is age6months,MPTP20mg/kg, probenecid200mg/kg, administration period5weeks. Ethology study find swimming and AFP changes both significant, with coefficient correlation0.388,0.450and P value0.005,0.0012.2, The coefficient correlations between TH CPC and DA, Ach,8-OHdG,UA,EGF are0.07,0.05,-0.67,0.23,0.68,with P value0.000、0.110、0.7150、000、0.654. And the area under curve(AUC) are separately0.53,0.53,0.82,0.55,0.82. Conclusions1、Administration period is proved the most important fact of mouse model in PD. It can probably be used to reduce the drug dosage.2. The AUC of8-OhdG and EGF are within0.7and0.9.It is considered that they are quite precise in diagnosis of PD in mouse model.