Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion
Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion
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DOI：
10.1016/j.brainres.2010.01.079
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发表时间：
2010-04
期刊：
影响因子：
2.9
通讯作者：
Xi-hong Ye;Yan Wu;Peipei Guo;Jie Wang;Shi-ying Yuan;You Shang;S. Yao
中科院分区：
文献类型：
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作者：
Xi-hong Ye;Yan Wu;Peipei Guo;Jie Wang;Shi-ying Yuan;You Shang;S. Yao
炎症，这是已知的是有害的神经系统的结果在急性期缺血后，提供了一个潜在的预防或治疗急性中风的方法。脂氧素是内源性脂氧合酶衍生的类花生酸，在一系列病理生理过程中引起保护作用。本实验观察了脂氧素A4的稳定合成类似物5（S），6（R）-脂氧素A4甲酯（LXA 4 ME）对大鼠脑缺血再灌注损伤的保护作用。采用大脑中动脉阻断法制备大鼠局灶性脑缺血模型。脑缺血发作后立即脑室注射LXA 4 ME可改善神经功能障碍，减少梗死体积，减少神经元凋亡。此外，LXA 4 ME可抑制中性粒细胞浸润和脂质过氧化水平，抑制小胶质细胞和星形胶质细胞的活化，降低促炎细胞因子TNF-α和IL-1β的表达，上调抗炎细胞因子IL-10和TGF-β1的表达。此外，NF-κ B的活化被LXA 4 ME处理抑制。这些结果表明，LXA 4 ME的治疗提供了强大的神经保护作用，对脑缺血再灌注损伤，这些作用可能与其抗炎特性。
Inflammation, which is known to be detrimental to the neurological outcome during the acute phase after ischemia, provides a potential preventative or therapeutic approach for acute stroke. Lipoxins are endogenous lipoxygenase derived eicosanoids and evokes protective actions in a range of pathophysiologic processes. Here, we evaluated the efficacy of 5 (S), 6 (R)-lipoxin A4methyl ester (LXA4ME), a stable synthetic analogue of lipoxin A4in cerebral ischemia reperfusion injury in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2h. Intracerebroventricular administration of LXA4ME immediately after onset of ischemia ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal apoptosis. Moreover, Treatment with LXA4ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-α and IL-1β; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-β1 in the ischemic brain. In addition, activation of NF-κΒ was inhibited by LXA4ME treatment. These results demonstrate that treatment of LXA4ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.