Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia
Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia
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DOI：
10.1016/j.cyto.2004.12.014
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发表时间：
2005-05-07
期刊：
影响因子：
3.8
通讯作者：
Villa, P
中科院分区：
文献类型：
--
作者：
Garau, A;Bertini, R;Villa, P
多形核中性粒细胞（PMN）的浸润被认为在缺血性脑损伤中发挥作用。本研究调查了 Repertaxin（一种针对炎症趋化因子 CXC 配体 8 (CXCL8)/白细胞介素 8 (IL-8) 受体的新型非竞争性变构抑制剂）对大鼠 PMN 浸润和组织损伤的影响。通过大脑中动脉的永久或短暂闭塞诱导脑缺血，并在 24 小时后评估髓过氧化物酶活性（PMN 浸润的标志物）和梗塞体积。 Repertaxin (15 mg/kg) 在缺血时全身给药，每 2 小时一次，共四次。在永久性缺血中，repertaxin 将大脑皮质中的 PMN 浸润减少了 40%，但并没有限制组织损伤。在短暂性缺血（90 分钟缺血后再灌注）中，repertaxin 可抑制 54% 的 PMN 浸润，并提供 44% 的组织损伤保护。再灌注时甚至再灌注 2 小时给予 Repertaxin 也具有抗炎和神经保护作用。 repertaxin 的保护作用不会干扰趋化因子的脑水平。由于在两个模型中 PMN 浸润及其对 repertaxin 的抑制作用相当，我们得出结论，再灌注诱导 PMN 激活，而 repertaxin 对 CXCL8 的抑制可能在短暂性缺血中具有药理学意义。 (c) 2005 Elsevier Ltd. 保留所有权利。
Infiltration of polymorphonuclear neutrophils (PMNs) is thought to play a role in ischemic brain damage. The present study investigated the effect of repertaxin, a new noncompetitive allosteric inhibitor for the receptors of the inflammatory chemokine CXC ligand 8 (CXCL8)/interleukin-8 (IL-8), on PMN infiltration and tissue injury in rats. Cerebral ischemia was induced by permanent or transient occlusion of the middle cerebral artery and myeloperoxidase activity, a marker of PMN infiltration, and infarct volume were evaluated 24 h later. Repertaxin (15 mg/kg) was administered systemically at the time of ischemia and every 2 h for four times. In permanent ischemia repertaxin reduced PMN infiltration by 40% in the brain cortex but did not limit tissue damage. In transient ischemia (90-min ischemia followed by reperfusion), repertaxin inhibited PMN infiltration by 54% and gave 44% protection from tissue damage. Repertaxin had anti-inflammatory and neuroprotective effects also when given at reperfusion and even at 2 h of reperfusion. The protective effect of repertaxin did not interfere with brain levels of the chemokine.Since the PMN infiltration and its inhibition by repertaxin were comparable in the two models we conclude that reperfusion induces PMN activation, and inhibition of CXCL8 by repertaxin might be of pharmacological interest in transient ischemia. (c) 2005 Elsevier Ltd. All rights reserved.