肉桂酰雷公藤甲素调节ROS/NF-κB信号通路对IFN-γ诱导的肾小球系膜细胞炎症的影响OA

Objective To explore the protective effect and potential molecular mechanism of cinnamyl triptolide(T32)on glomerular mesangial cell inflammation.Methods Primary cultures of glomerular mesangial cells were isolated and purified from lupus nephritis mice,and they were randomly divided into control group and interferon-γ(IFN-γ)stimulation group(IFN-γ 1000U/ml,24h),pyrrolidine dithiocarbamate(PDTC)intervention group(PDTC 10μmol/ml+IFN-γ 1000U/ml,24h),T32 intervention group(T32 10ng/ml+IFN-γ 1000U/ml,24h).The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ-inducible protein-10(IP-10),reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione(GSH),cytochrome C oxidase subunitⅠ(COXⅠ)gene expressions and the nuclear translocation of nuclear factor κB(NF-κB)in each group were compared.Results The levels of TNF-α,IL-6,ROS,COXⅠ mRNA expressions,and mRNA and protein expression levels of IP-10 in IFN-γ stimulation group were significantly higher than those in control group,while the SOD activity and GSH level were significantly lower than those in control group(P<0.05).The levels of TNF-α,IL-6,ROS,COXⅠ mRNA expressions,and mRNA and protein expression levels of IP-10 in PDTC intervention group and T32 intervention group were significantly lower than those in IFN-γ stimulation group,while SOD activity and GSH level were significantly higher than those in IFN-γ stimulation group(P<0.05).The results of immunofluorescence staining showed that after IFN-γ stimulated the cells,the NF-κB protein was converted to intracellular expression(P<0.01).After intervention with PDTC and T32,the nuclear translocation of NF-κB protein was effectively inhibited(P<0.01).Conclusion T32 inhibits the expression of IP-10 in glomerular mesangial cells by reducing ROS production and down-regulating NF-κB signaling pathway,thereby alleviating the IFN-γ-induced inflammatory response.