【摘要】 目的 探究用dBET1降解溴结构域蛋白4(BRD4)能否抑制α突触核蛋白(α-syn)寡聚体导致的神经炎症及氧化应激。方法 dBET1与α-syn寡聚体共同处理BV2细胞或SH-SY5Y细胞，分为对照组、α-syn组、α-syn+500 nmol/L dBET1组，α-syn+1000 nmol/L dBET1组，1000 nmol/L dBET1组。定量聚合酶链反应检测炎性因子及抗炎因子，蛋白质免疫印迹检测BRD4、核因子E2相关因子2(Nrf2)、磷酸化核转录因子κB(p-NF-κB)及磷酸化α-syn(p-α-synuclein)等。结果 α-syn+1000 nmol/L dBET1组炎性因子mRNA、BRD4、p-NF-κB、p-α-synuclein表达低于α-syn组，而抗炎因子mRNA、细胞核Nrf2表达显著高于α-syn组[(2.02±0.14)vs(0.96±0.24),P<0.05]。结论 dBET1通过p-NF-κB及Nrf2在一定程度上能抑制α-syn导致的神经炎症及氧化应激等，为进一步运用于治疗帕金森病等疾病提供理论基础。更多还原

【Abstract】 Objective To investigate whether degradation of bromodomain-containing protein 4(BRD4) protein with dBET1 can inhibit neuroinflammation and oxidative stress caused by α-synuclein(α-syn) oligomers.Methods After BV2 cells or SH-SY5Y cells were treated with dBET1 and α-syn oligomers, the cells were divided into Control group, α-syn group, α-syn+500 and 1000 nmol/L dBET1 groups, and dBET1 group(1000 nmol/L).Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of inflammatory factors and anti-inflammatory factors, and Western blotting was employed to measure the expression of BRD4,nuclear factor 2 associated factor 2(Nrf2),phosphorylated nuclear transcription factor-κB(p-NF-κB) and phosphorylated α-synuclein(p-α-synuclein).Results The α-syn+1000 nmol/L dBET1 group had lower mRNA levels of inflammatory factors and reduced protein levels of BRD4,p-NF-κB and p-α-synuclein, but higher mRNA levels of anti-inflammatory factors and decreased Nrf2 protein level(2.02±0.14 vs 0.96±0.24,P<0.05) when compared with the α-syn group.Conclusion dBET1 can inhibit neuroinflammation and oxidative stress caused by α-synuclein through p-NF-κB and Nrf2 to a certain extent, which further provides a theoretical basis for its application in the treatment of Parkinson’s disease.更多还原