The Immunologic Mechanism Of Tregs And Fas/FasL In Dopamine Neurons Of Parkinson's Disease

Objective: 1)To explore the relationship between the values of blood routine examination or ratios of blood cells and risk or development of Parkinson's Disease(PD).2)To study the variation and clinical significance of CD3+%,CD4+%,CD8+%,CD19+%,CD56+%,Fas(%),and Tregs in Parkinson' s disease(PD);3)To investigate the expression of death receptor(Fas)and Tregs in an animal model of Parkinson's disease(PD).To investigate the role of Fas and Tregs in the pathogenesis of PD.Methods: 1)Medical records of 453 PD patients and 436 controls were reviewed retrospectively.All patients were diagnosed between June 2002 and July 2017.The development of PD was quantified by modified Hoehn-Yahr Scale.In the patients and control individuals,values of blood routine examination were reviewed,and ratios of blood cells were calculated.After the adjustments,the 453 patients with PD were compared with the 436 comorbidities-matched control individuals.Conditional logistic regression analysis was performed to explore the relationship between blood values or ratios and risk of PD.And ordinal logistic regression analysis was performed to explore relationship between values or ratios and development of PD;2)Fluorescent staining was used to determine CD3+%,CD4+%,CD8+%,CD19+%,CD56+%,Fas(%),and Tregs in peripheral blood of 83 patients with PD in both Victoria and Han and compared with 100 healthy controls.And analyze the correlation among different ethnic groups,different medications,different course of disease and HY scores and changes of each subgroup of cells;3)PD model was made by injecting 6-OHDA,which was treated with Madopar.Normal control group(n=10),sham operation group(n=10),PD model group(n=20)and Madopar intervention group(n=20)were established.The rotation behaviors of the rats in each group were observed and the substantia nigra tissue was extracted.The changes of Fas,FasL and FoxP3 were detected by immunoblotting.The changes of Fas,FasL,FoxP3 and TH were detected by immunohistochemistry.Results: 1)Of the 453 PD patients,203 were female,and the median age was 63;Of the 436 controls,214 were female,and the median age was 61.Decreased levels of lymphocyte-platelet ratio,mean corpuscular hemoglobin concentration and plateletcrit,increased levels of platelet-red blood cell ratio and platelet distribution width were linked with increased risk of PD.And increased levels of neutrophil-lymphocyte ratio,duration of PD,decreased levels of neutrophil-platelet ratio were associated with development of PD.2)The CD3+,CD4+ and CD8+T lymphocytes in peripheral blood of Parkinson's disease patients were significantly lower than those in the control group,while B lymphocytes were not significantly different from those in the control group,while NK cells,Fas(%)and Tregs cells increased.There was no significant change in the number of lymphocyte subgroups and NK cells in the Uygur patients compared with the Han patients.The Fas and Tregs cells in the drug group were lower than those in the non taking group.The CD3+T lymphocyte subsets were correlated with the age of PD patients,the B cell subsets and the duration of PD patients.There was a certain correlation between Fas lymphocyte and Tregs cell and severity.3)Compared with the normal group,the expression of TH in the model group decreased,and the expression of Fas,FasL and FoxP3(Tregs)cells in the substantia nigra region increased(P<0.01).Conclusion: Peripheral blood lymphocyte changes are associated with PD.The peripheral blood lymphocytes,NK cells and Fas expression levels of PD patients were changed.Changes in peripheral blood lymphocyte subsets and Fas may help assess the progression of PD.Abnormal expression of Fas and Tregs in the nigrostriatal tissue may play an important role in the pathogenesis of PD.