血小板因子4通过Trem2调控AD细胞模型中小胶质细胞极化促进Aβ清除的研究OA

Objective:To investigate the potential impact of platelet factor 4(PF4)on the M1/M2 polarization of microglia in an Alzheimer's disease(AD)cell model and its possible molecular mechanisms.Methods:An AD cell model was induced by treating BV2 microglial cells with A β 1-42,followed by PF4 intervention.Furthermore,Trem2 expression was knocked down in BV2 cells through Trem2-siRNA transfection.Cell viability was assessed using the CCK8 assay;levels of TNF-α,IL-6,and IL-1 β were measured by ELISA;the expressions of Trem2,iNOS,and Arg1 were detected via double-label immunofluorescence and Western blot analyses;mRNA levels of Trem2,iNOS,Arg1,TNF-α,and IL-10 were determined by RT-qPCR;and phagocytic function was evaluated using flow cytometry.Results:Compared with the control group,the A β 1-42 group exhibited significantly elevated expression levels of M1 phenotype markers(iNOS,TNF-α,IL-1 β)and IL-6,along with markedly decreased expression of M2 phenotype markers(Arg1,IL-10)and Trem2.In contrast,the(Aβ1-42+PF4)group showed reduced expression of M1 phenotype markers(iNOS,TNF-α,IL-1β)and IL-6,increased expression of M2 phenotype markers(Arg1,IL-10)and Trem2,and enhanced phagocytic capacity for A β 1-42 compared with the Aβ1-42 group.However,compared with the(Trem2-siRNA+Aβ1-42)group,PF4 failed to exert the aforementioned effects in BV2 cells in the(Trem2-siRNA+Aβ1-42+PF4)group.Conclusion:PF4 can regulate microglial polarization via Trem2,alleviate AD-related neuroinflammation,and promote the clearance of Aβ1-42.