沉默信息调节因子1与Toll样受体4信号通路在1-甲基-4-苯基-吡啶离子帕金森病细胞模型炎症反应中的作用OA

Objective To investigate the role of the silent information regulator 1(Sirt1)-Toll-like receptor 4(TLR4)signaling pathway in inflammatory response in a cell model of Parkinson disease(PD)induced by 1-methyl-4-phenyl pyridine ion(MPP+).Methods SH-SY5Y cells were treated with MPP+to establish a cell model of PD,and resveratrol(RV)and EX527 were used to modulate the expression of Sirt1 in the cell model.SH-SY5Y cells were divided into control group,model group(MPP+group),activator group(RV+MPP+group),and inhibitor group(EX527+MPP+group),and the cells were cultured in a high-glucose medium.CCK-8 assay was used to assess the cytotoxicity of MPP+,RV,and EX527,and finally MPP+(0.75 mmol/L),RV(20 μmol/L),and EX527(80 μmol/L)were selected for 48 hours of intervention.Western blotting was used to measure the expression levels of tyrosine hydroxylase(TH),Sirt1,and the inflammation-related protein TLR4;ELISA was used to measure the levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in cell supernatant;immunofluorescence assay was used to measure the expression of TH,Sirt1,TLR4,and related inflammatory factors in cells.Results Compared with the control group,the MPP+group had significant reductions in the expression levels of TH and Sirt1 and a significant increase in the expression level of TLR4(P<0.05);compared with the MPP+group,the RV+MPP+group had significant increases in the expression levels of TH and Sirt1 and a significant reduction in the expression level of TLR4(P<0.05);compared with the control group and the RV+MPP+group,the EX527+MPP+group had significant reductions in the expression levels of TH and Sirt1 and a significant increase in the expression level of TLR4(P<0.05).ELISA showed that compared with the control group and the RV+MPP+group,the MPP+group and the EX527+MPP+group had significant increases in the levels of IL-1β,IL-6,and TNF-α(P<0.05),and compared with the MPP+group,the EX527+MPP+group had significant increases in the levels of IL-1β,IL-6,and TNF-α(P<0.05).Immunofluorescence assay showed that compared with the control group,the MPP+group had significant reductions in the expression levels of TH and Sirt1 and significant increases in the expression levels of TLR4 and the inflammatory factors IL-1β and TNF-α(P<0.01);compared with the MPP+group,the RV+MPP+group had significant increases in the expression levels of TH and Sirt1 and significant reductions in the expression levels of TLR4,IL-1β,and TNF-α(P<0.01);compared with the MPP+group,the EX527+MPP+group had significant reductions in the expression levels of TH and Sirt1 and significant increases in the expression levels of TLR4 and the inflammatory factors IL-1β and TNF-α(P<0.01).Conclusions The Sirt1-TLR4 signaling pathway is significantly associated with the process of neuroinflammation in PD and may play a role in the development and progression of the disease.