中文摘要：

目的探讨肝X受体（LXR）激动剂T0901317上调人肾小球内皮细胞（HRGEC）血栓调节蛋白（TM）表达的机制和作用。方法 Western blot检测25 mmol高糖和2μmol T0901317刺激后的HRGEC上IκBα、磷酸化IκBα、核转录因子-κB（NF-κB）p65、磷酸化NF-κB p65表达;免疫共沉淀法检测LXR与P300之间有无结合;重组腺病毒Ad TMsh RNA转染HRGEC,观察其对高糖下HRGEC分泌炎症介质的影响。结果T0901317能显著降低高糖刺激后的IκBα和NF-κB p65磷酸化（P〈0.05）,LXR-α沉默后NF-κB活性增强;2μmol T0901317刺激HRGEC 24 h后以Co-IP检测LXR与P300的表达上调;T0901317明显抑制高糖刺激下的HRGEC培养上清中TNF-α、IL-1β浓度（P〈0.05）,Ad TMsh RNA转染HRGEC后,有或无T0901317刺激,HRGEC培养上清中TNF-α、IL-1β浓度与高糖组比较,差异无统计学意义（P〉0.05）。结论LXR可能通过与P300发生相互作用阻断了NF-κB与P300之间的竞争性结合而提高TM的表达并抑制炎症介质的分泌。

英文摘要：

Objective To explore the effect of liver X receptor（LXR） agonist T0901317 on thrombomodulin（TM） expression in human glomerular endothelial cells（HUGECs） and its mechanism.Methods Western blot was used to detect the expressions of IκBα, p-IκBα, nuclear transcription factor-κB（NF-κβ） p65 and p-NF-κB p65 in HUGECs stimulated by 25 mmol high glucose and 2 μmol T0901317. The interaction between LXR and the transcriptional coactivator p300 in HUGECs was detected using co-immunoprecipitation（Co-IP） assay. The concentrations of IL-1β and TNF-α in the supernatant of HUGECs transfected with or without Ad TMsh RNA were determined using commercially available ELISA kits. Results T0901317（2 μmol） significantly reduced the phosphorylation of IκBα and NF-κB p65 in the HUGECs stimulated by high glucose（P 〈0.05）. The activity of NF-κB was increased by LXR-α silencing despite the presence of T0901317. Co-IP revealed up-regulation of LXP and p300 in the HUGECs 24 h after stimulation by 2 μmol T0901317. T0901317 inhibited the secretion of high glucose-induced inflammatory cytokines such as TNF-α and IL-1β in the HUGECs（P 〈0.05）. The levels of TNF-α and IL-1β were increased by TM silencing with Ad TMsh RNA despite the presence of T0901317, but the differences were not significant（P 〉0.05）. Conclusions LXR agonist increases TM expression and inhibits secretion of inflammatory mediators probably by competitively blocking the interaction between NF-κB and p300 through interaction with p300.