HMGB1-TLR4轴及其下游信号因子在帕金森病患者中的变化及其意义

Changes of HMGB1-TLR4 axis and its downstream signal factor in patients with Parkinson′s disease and their significance

目的检测帕金森病患者血清中高迁移率族蛋白B1(HMGB1)和Toll样受体4(TLR4)及下游信号因子髓样分化因子(My D88)、核因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)的表达水平,并探讨其和帕金森病发生、进展的关系。方法选择帕金森病患者120例,健康志愿者100例,应用双抗体夹心酶联免疫吸附实验(ELISA)测定两组患者血清中HMGB1和TLR4的表达水平,分析帕金森患者血清HMGB1和TLR4蛋白的表达与帕金森病患者分期、病程、药物治疗有效性、临床分型的关系,同时分析HMGB1-TLR4轴下游关键因子My D88、NF-κB、TNF-α的表达。结果帕金森病患者外周血中HMGB1和TLR4相比健康志愿者呈现高表达,药物控制不良的患者HMGB1和TLR4的表达显著高于药物控制良好(稳定型)的患者,且分期越高的患者HMGB1和TLR4的表达越高,病程>4年的患者HMGB1和TLR4的表达显著高于病程<4年的患者,但是帕金森病分型中混合性、震颤型和强直型患者HMGB1和TLR4的表达未见明显差异。下游信号因子My D88、NF-κB、TNF-α在帕金森病中高表达。结论 HMGB1-TLR4轴及下游因子在帕金森病中高表达,对于帕金森的辅助诊断和治疗有着很高的意义。

Objective To detect expression levels of serum high mobility group protein BI(HMGB1),Toll like receptor 4(TLR4)and downstream signal factors myeloid differentiation factor(MyD88),nuclear factorκB(NF-κB)and tumor necrosis factorα(TNF-α)in patients with Parkinson′s disease,and to explore the associ-ation of these biomarkers with the occurrence and progression of Parkinson′s disease.Methods 120 patients with Parkinson′s disease and 100 healthy volunteers were selected.The expression levels of HMGB1 and TLR4 in the two groups were detected by double antibody sandwich enzyme-linked immunosorbent assay(ELISA).The correla-tion of expression of MyD88,NF-κB and TNF-α,and the key factors of the HMGB1-TLR4 axis was analyzed.The association of expressions of serum HMGB1 and TLR4 protein in patients with Parkinson′s disease with stages,course of disease,efficacy of treatment and clinical typing.Results As compared with those in healthy volun-teers,higher expressions of peripheral blood HMGB1 and TLR4 in patients with Parkinson′s disease.Expressions of HMGB1 and TLR4 were significantly higher in patients unresponsive to therapy than in those responsive well to therapy(stable).The higher the staging,the higher the expressions of HMGB1 and TLR4 expression.Expressions of HMGB1 and TLR4 were significantly higher in patients with a disease course of longer than 4 years than in those with a course shorter than 4 years.Expressions of HMGB1 and TLR4 did not differ significantly among mixed type,rigid type,and tremor type.Downstream signal factors MyD88,NF-κB,and TNF-alpha were highly expressed in Parkinson′s disease.Conclusions HMGB1-TLR4 axis and its downstream factors are highly expressed in Parkin-son′s disease,which is of great significance for related diagnosis and treatment of Parkinson′s disease.