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首页> 外文期刊>International immunopharmacology >PG490-88, a derivative of triptolide, suppresses ischemia/reperfusion-induced lung damage by maintaining tight junction barriers and targeting multiple signaling pathways
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PG490-88, a derivative of triptolide, suppresses ischemia/reperfusion-induced lung damage by maintaining tight junction barriers and targeting multiple signaling pathways

机译:PG490-88,雷公藤内酯的衍生物,通过保持紧密的结屏障和靶向多个信号通路来抑制缺血/再灌注诱导的肺部损伤

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摘要

Previous studies demonstrated that triptolide (PG490) has many anti-inflammatory and immunosuppressive effects. However, little is known about the effect of PG490-88 (a water-soluble derivative of triptolide) on ischemia/reperfusion (I/R)-induced acute lung injury. We assessed the effects of PG490-88 on I/R-induced acute lung injury in rats and on hypoxia/reoxygenation (H/R) in a line of murine epithelial cells. Isolated perfused rat lungs were subjected to 40 min of ischemia, followed by 60 min of reperfusion to induce I/R injury. Induction of I/R led to lung edema, elevated pulmonary arterial pressure, histological evidence of lung inflammation, oxidative stress, and increased levels of TNF-alpha and CINC-1 in bronchoalveolar lavage fluid. PG490-88 significantly suppressed all of these responses. Additionally, induction of I/R reduced the expression of claudin-4, occludin, and 20-1, and increased apoptosis in lung tissue. PG490-88 also significantly suppressed these effects. I/R reduced the levels of I kappa B-alpha and MKP-1, and increased the levels of nuclear NF-kappa B and mitogen-activated protein kinase in lung tissue, and PG490-88 suppressed these effects. In vitro studies using mouse lung alveolar epithelial cells indicated that H/R increased the levels of phosphorylated p65 and MIP-2, but decreased the level of I kappa B-alpha. PG490-88 also suppressed these effects. In I/R damaged lungs, PG490-88 suppresses the inflammatory response, disruption of tight junction structure, and apoptosis. PG490-88 has the potential as a prophylactic agent to prevent I/R-induced lung injury.
机译:以前的研究表明,雷公藤内酯(PG490)具有许多抗炎和免疫抑制作用。然而,关于PG490-88(Triptolide的水溶性衍生物)对缺血/再灌注(I / R)引起的急性肺损伤的影响几乎熟知。我们评估了PG490-88对大鼠I / R诱导的急性肺损伤的影响和鼠上皮细胞系中的缺氧/雷诺(H / R)。将分离的灌注大鼠肺进行40分钟的缺血,然后再灌注60分钟以诱导I / R损伤。 I / R诱导导致肺水肿,肺动脉压升高,肺炎的组织学证据,氧化胁迫和肺结气血液血液灌洗液中的TNF-α和CINC-1水平增加。 PG490-88显着抑制了所有这些反应。另外,I / R的诱导降低了Claudin-4,occludin和20-1的表达,并增加了肺组织中的细胞凋亡。 PG490-88也显着抑制了这些效果。 I / R降低了I Kappa B-α和MKP-1的水平,并增加了肺组织中核NF-κB和丝裂原活化蛋白激酶的水平,PG490-88抑制了这些效果。使用小鼠肺肺泡上皮细胞的体外研究表明H / R增加了磷酸化P65和MIP-2的水平,但降低了IκB-α的水平。 PG490-88还抑制了这些效果。在I / R受损的肺部中,PG490-88抑制了炎症反应,严重接合结构的破坏和细胞凋亡。 PG490-88具有作为预防剂的潜力,以防止I / R诱导的肺损伤。

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