中国药理学通报2024，Vol.40Issue(8)：1510-1516,7.DOI:10.12360/CPB202402037
SIRT3抑制PARP-1活性缓解多巴胺能神经元炎症损伤
SIRT3 expression alleviates inflammatory damage of dopaminergic neurons by inhibiting PARP-1 activity
摘要
Abstract
Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.关键词
多巴胺能神经元/SIRT3/聚腺苷二磷酸核糖聚合酶-1/神经炎症/核转录因子-κB/活性氧Key words
dopaminergic neuron/SIRT3/PARP-1/neuroinflammation/nuclear transcription factor-κB/re-active oxygen species分类
医药卫生引用本文复制引用
蒋德旗,梁瑞兰,蒋丽林,勾玲,徐兰程..SIRT3抑制PARP-1活性缓解多巴胺能神经元炎症损伤[J].中国药理学通报,2024,40(8):1510-1516,7.基金项目
广西自然科学基金面上项目(No 2021GXNSFAA220001) （No 2021GXNSFAA220001）
玉林师范学院高层次人才科研项目(No G2024ZK03) （No G2024ZK03）
