本文選題：人腎小球內(nèi)皮細(xì)胞　切入點(diǎn)：肝X受體　出處：《中國(guó)現(xiàn)代醫(yī)學(xué)雜志》2016年05期 　論文類型：期刊論文

【摘要】：目的探討肝X受體(LXR)激動(dòng)劑T0901317上調(diào)人腎小球內(nèi)皮細(xì)胞(HRGEC)血栓調(diào)節(jié)蛋白(TM)表達(dá)的機(jī)制和作用。方法 Western blot檢測(cè)25 mmol高糖和2μmol T0901317刺激后的HRGEC上IκBα、磷酸化IκBα、核轉(zhuǎn)錄因子-κB(NF-κB)p65、磷酸化NF-κB p65表達(dá);免疫共沉淀法檢測(cè)LXR與P300之間有無結(jié)合;重組腺病毒Ad TMsh RNA轉(zhuǎn)染HRGEC,觀察其對(duì)高糖下HRGEC分泌炎癥介質(zhì)的影響。結(jié)果T0901317能顯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活性增強(qiáng);2μmol T0901317刺激HRGEC 24 h后以Co-IP檢測(cè)LXR與P300的表達(dá)上調(diào);T0901317明顯抑制高糖刺激下的HRGEC培養(yǎng)上清中TNF-α、IL-1β濃度(P0.05),Ad TMsh RNA轉(zhuǎn)染HRGEC后,有或無T0901317刺激,HRGEC培養(yǎng)上清中TNF-α、IL-1β濃度與高糖組比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論LXR可能通過與P300發(fā)生相互作用阻斷了NF-κB與P300之間的競(jìng)爭(zhēng)性結(jié)合而提高TM的表達(dá)并抑制炎癥介質(zhì)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 偽, phosphorylated I 魏 B 偽 and transcription factor I 魏 B 偽, phosphorylated I 魏 B 偽 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 偽 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- 偽 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- 偽 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.
【作者單位】： 四川省醫(yī)學(xué)科學(xué)院(四川省人民醫(yī)院)腎內(nèi)科;四川省成都市第二人民醫(yī)院腎內(nèi)科;
【基金】：國(guó)家自然科學(xué)基金(No:81170680) 四川省科技廳課題(No:2013JY0141)
【分類號(hào)】：R692
，

本文編號(hào)：1595854