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Neuroprotective effects of SMAds in a rat model of cerebral ischemia/reperfusion

机译:SMAds对大鼠脑缺血/再灌注模型的神经保护作用

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摘要

Previous studies have shown that up-regulation of transforming growth factorβ1 results in neuroprotective effects. However, the role of the transforming growth factorβ1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inlfammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phos-phorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats viadelivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor ne-crosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These ifndings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inlfamma-tory and anti-apoptotic pathways.
机译:先前的研究表明,转化生长因子β1的上调可导致神经保护作用。然而,缺血/再灌注后转化生长因子β1下游分子SMAD2 / 3的作用尚不清楚。在这里,我们通过分析SMAD2 / 3表达与大鼠脑缺血/再灌注模型的脑细胞凋亡和炎症信号之间的关系,研究了SMAD2 / 3的神经保护作用。在脑缺血/再灌注后6小时,缺血半影中SMAD2 / 3 mRNA的水平上调,在72小时后达到峰值,然后在7天时降低。在上述时间点磷酸化的SMAD2 / 3蛋白水平与mRNA水平一致。通过递送包含SMAD3基因的腺相关病毒,在缺血/再灌注模型大鼠脑中SMAD3的过表达可降低肿瘤坏死因子-α和白介素1βmRNA的水平,下调pro-pro的表达。凋亡基因capase-3,并上调抗凋亡蛋白Bcl-2的表达。 SMAD3蛋白水平与细胞凋亡呈负相关。这些结果表明,SMAD3通过抗炎症过程和抗凋亡途径对缺血/再灌注后的大脑表现出神经保护作用。

著录项

  • 来源
    《中国神经再生研究(英文版)》 |2015年第3期|438-444|共7页
  • 作者单位

    Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China;

    Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China;

    Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin Province, China;

    Department of Neurology, Afifliated Hospital of Yanbian University, Yanbian, Jilin Province, China;

    Department of Hepatic-Biliary-Pancreatic Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China;

    Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China;

    Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China;

  • 收录信息 中国科学引文数据库(CSCD);中国科技论文与引文数据库(CSTPCD);
  • 原文格式 PDF
  • 正文语种 eng
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  • 入库时间 2022-08-19 03:44:31
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