肝X受体激动剂上调人肾小球内皮细胞血栓调节蛋白表达的机制和作用

发布时间：2018-03-11 01:00

  本文选题：人肾小球内皮细胞　切入点：肝X受体　出处：《中国现代医学杂志》2016年05期 　论文类型：期刊论文

【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(P0.05),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(P0.05),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(P0.05)。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。
[Abstract]:Objective to investigate the mechanism and role of hepatic X receptor agonist T0901317 in up-regulating the expression of thrombomodulin (TMN) in human glomerular endothelial cells (HRGECs). Methods Western blot was used to detect I 魏 B 伪, phosphorylated I 魏 B 伪 and transcription factor I 魏 B 伪, phosphorylated I 魏 B 伪 in HRGEC stimulated by 25 mmol high glucose and 2 渭 mol T0901317. NF- 魏 B p65, phosphorylated NF- 魏 B p65; The binding between LXR and P300 was detected by immunoprecipitation. The effect of recombinant adenovirus Ad TMsh RNA on the secretion of inflammatory mediators by HRGEC under high glucose was observed. Results T0901317 significantly decreased I 魏 B 伪 and NF- 魏 B p65 phosphorylated P0.05A silencing with 2 渭 mol T0901317 for 24 h after HRGEC was stimulated with Co-IP. The expression of LXR and P300 was up-regulated. T0901317 significantly inhibited the concentration of TNF- 伪 LXR IL-1 尾 in the supernatant of HRGEC cultured with high glucose. P0.05A Ad TMsh RNA was transfected into HRGEC. The concentration of TNF- 伪 and IL-1 尾 in the supernatant of HRGEC stimulated by T0901317 or without T0901317 was compared with that in high glucose group. Conclusion LXR may increase the expression of TM and inhibit the secretion of inflammatory mediators by blocking the competitive binding between NF- 魏 B and P300 by interacting with P300.
【作者单位】： 四川省医学科学院(四川省人民医院)肾内科;四川省成都市第二人民医院肾内科;
【基金】：国家自然科学基金(No:81170680) 四川省科技厅课题(No:2013JY0141)
【分类号】：R692
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