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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia.
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Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia.

机译:肿瘤坏死因子-α中和通过抑制短暂性局灶性脑缺血后基质金属蛋白酶的产生减少脑水肿。

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After focal cerebral ischemia, tumor necrosis factor-alpha deteriorates cerebral edema and survival rate. Therefore, tumor necrosis factor-alpha neutralization could reduce cerebral microvascular permeability in acute cerebral ischemia. Left middle cerebral artery occlusion for 120 mins followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Antirat tumor necrosis factor-alpha neutralizing monoclonal antibody with a rat IgG Fc portion (15 mg/kg) was infused intravenously right after reperfusion. Stroke index score, infarct volume, cerebral specific gravity, and the endogenous expression of tumor necrosis factor-alpha, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in the brain tissue were quantified in the ischemic and matched contralateral nonischemic hemisphere. In the antitumor necrosis factor-alpha neutralizing antibody-treated rats, infarct volume was significantly reduced (P=0.014, n=7; respectively), and cerebral specific gravity was dramatically increased in the cortex and caudate putamen (P<0.001, n=7; respectively) in association with a reduction in MMP-9 and membrane type 1-MMP upregulation. Tumor necrosis factor-alpha in the brain tissue was significantly elevated in the ischemic hemisphere 6 h after reperfusion in the nonspecific IgG-treated rats (P=0.021, n=7) and was decreased in the antitumor necrosis factor-alpha neutralizing antibody-treated rats (P=0.001, n=7). Postreperfusion treatment with antirat tumor necrosis factor-alpha neutralizing antibody reduced brain infarct volume and cerebral edema, which is likely mediated by a reduction in MMP upregulation.
机译:局灶性脑缺血后,肿瘤坏死因子-α使脑水肿和生存率恶化。因此,肿瘤坏死因子-α中和可以降低急性脑缺血时脑微血管的通透性。氟烷麻醉下,在Sprague-Dawley大鼠中,通过线法进行左大脑中动脉闭塞120分钟,然后再灌注。再灌注后立即静脉输注具有大鼠IgG Fc部分(15 mg / kg)的Antirat肿瘤坏死因子-α中和单克隆抗体。在缺血和缺血性脑卒中中,对脑组织中风指数评分,梗塞体积,脑比重以及肿瘤坏死因子-α,基质金属蛋白酶(MMP)-2,MMP-9和膜型1-MMP的内源表达进行定量。匹配对侧非缺血性半球。在抗肿瘤坏死因子-α中和抗体治疗的大鼠中,梗塞体积显着减少(P = 0.014,n = 7;分别),并且皮层和尾状壳中脑比重显着增加(P <0.001,n = 7;分别)与减少MMP-9和1型MMP膜上调相关。在非特异性IgG处理的大鼠中,再灌注后6小时,缺血半球中脑组织中的肿瘤坏死因子-α显着升高(P = 0.021,n = 7),而在抗肿瘤坏死因子-α中和抗体处理后,脑组织中的肿瘤坏死因子-α降低大鼠(P = 0.001,n = 7)。用抗大鼠肿瘤坏死因子-α中和抗体进行灌注后治疗可减少脑梗死体积和脑水肿,这可能是由于MMP上调的减少所介导的。

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