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首页> 外文期刊>RSC Advances >IMM-H004, a coumarin derivative, attenuated brain ischemia/reperfusion injuries and subsequent inflammation in spontaneously hypertensive rats through inhibition of VCAM-1
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IMM-H004, a coumarin derivative, attenuated brain ischemia/reperfusion injuries and subsequent inflammation in spontaneously hypertensive rats through inhibition of VCAM-1

机译：IMM-H004是一种香豆素衍生物，可通过抑制VCAM-1减轻自发性高血压大鼠的脑缺血/再灌注损伤和随后的炎症

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Strokes are the leading cause of death and disability all over the world, however, there are few satisfactory therapies. IMM-H004 citrate (004), 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin, is a coumarin derivative which has potential therapeutic effects in brain ischemia with ambiguous mechanisms. We aim to study the anti-brain ischemia effect and mechanism of 004 in spontaneously hypertensive (SHR) rats. Adult male Wistar-Kyoto (WKY) rats and SHR rats were subjected to 24 h reperfusion after transient middle cerebral artery occlusion (tMCAO) for 1 h and were intravenously injected with 004 or Edaravone at the time of reperfusion. Behavioral scores, magnetic resonance imaging (MRI) and TTC staining were used to test the therapeutic effect of 004. To study the mechanism, the infiltration of leukocytes, the activation of microglia, blood viscosity, the expression of VCAM-1, MMPs and proteins involved in the MAPK/NF-κB pathway were researched. The results indicated that tMCAO/R induced serious injury, while 004 significantly alleviated the infarct volume and improved neurological deficits. 004 improved inflammatory processes, such as the enhancement of blood viscosity, expression of VCAM-1 and MMP2, release of TNF-α, IL-1β, IL-6 and IL-23, phosphorylation of JNK and p38 and translocation of NF-κB, which play crucial roles in brain I/R in SHR rats. An in vitro study also proved that 004 regulated JNK and NF-κB pathways and decreased the expression of VCAM-1, which eventually led to the suppression of neuroinflammation.
机译：中风是世界范围内导致死亡和致残的主要原因，但是，很少有令人满意的疗法。 IMM-H004柠檬酸盐（004），7-羟基-5-甲氧基-4-甲基-3-（4-甲基哌嗪-1-基）-香豆素，是一种香豆素衍生物，其在脑缺血中具有潜在的治疗作用，其机制尚不明确。我们旨在研究自发性高血压（SHR）大鼠的004的抗脑缺血作用及其机制。成年雄性Wistar-Kyoto（WKY）大鼠和SHR大鼠在短暂性中脑动脉闭塞（tMCAO）后进行1小时的24小时再灌注，并在再灌注时静脉注射004或依达拉奉。通过行为学评分，磁共振成像（MRI）和TTC染色来检验004的治疗效果。研究其机理，白细胞浸润，小胶质细胞活化，血液粘度，VCAM-1，MMPs和蛋白质的表达研究了参与MAPK /NF-κB途径的分子。结果表明，tMCAO / R引起严重损伤，而004则显着减轻了梗塞体积并改善了神经功能缺损。 004改善了炎症过程，例如提高血液粘度，VCAM-1和MMP2的表达，TNF-α，IL-1β，IL-6和IL-23的释放，JNK和p38的磷酸化以及NF-κB的易位，在SHR大鼠的大脑I / R中起关键作用。一项体外研究还证明004调节JNK和NF-κB通路并降低VCAM-1的表达，最终导致神经炎症的抑制。

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