Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats
Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats
复制标题
DOI：
10.3109/00207454.2014.980906
复制
发表时间：
2015-01-01
影响因子：
2.2
通讯作者：
Canas, C. A.
中科院分区：
文献类型：
--
作者：
Arango-Davila, C. A.;Vera, A.;Canas, C. A.
肿瘤坏死因子-α(TNF-α)是一种免疫调节和促炎细胞因子，与脑缺血引起的神经炎症和神经元损伤有关。目前的研究验证了抗肿瘤坏死因子-α制剂可能对脑梗塞具有保护作用的假设。在麻醉成年雄性Wistar大鼠(300-350g)上，用线栓法阻断大脑中动脉(MCAO)，造成短暂性局灶性脑缺血。抗肿瘤坏死因子-α的嵌合单抗(英夫利昔单抗-7 mg/kg)或肿瘤坏死因子-α受体-2与IgG1片段结晶区的嵌合融合蛋白(依那西普-5 mg/kg)可干扰肿瘤坏死因子-α的功能。两种药物均在诱导缺血后0h或6h内给药。2，3，5-三苯基四氮唑盐染法测定脑梗塞体积。再灌注24 h后，依那西普或英夫利昔单抗治疗组大鼠脑梗塞体积较未治疗组明显缩小。这些结果提示，抗肿瘤坏死因子-α制剂可以减轻大鼠局灶性脑缺血损伤。
Tumor Necrosis Factor-alpha (TNF-alpha) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-alpha agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-alpha function was interfered with either a chimeric monoclonal antibody against TNF-alpha (infliximab-7 mg/kg) aiming to TNF-alpha soluble and membrane-attached form; or a chimeric fusion protein of TNF-alpha receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-alpha soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-alpha agents may reduce focal ischemic injury in rats.