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首页> 外文期刊>The European Journal of Neuroscience >PPARgamma agonist pioglitazone rescues neuronal cell damage after transient global cerebral ischemia through matrix metalloproteinase inhibition.
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PPARgamma agonist pioglitazone rescues neuronal cell damage after transient global cerebral ischemia through matrix metalloproteinase inhibition.

机译：PPARγ激动剂吡格列酮可通过抑制基质金属蛋白酶挽救短暂性全脑缺血后的神经元细胞损伤。

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摘要

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, inhibits ischemia-induced injury in various tissues including neural tissue. Pioglitazone has also been shown to reduce matrix metalloproteinase (MMP) activity. Because MMP is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to test whether pioglitazone attenuates ischemic neuronal damage through MMP inhibition. C57BL/6 mice were subjected to global brain ischemia for 20 min. Animals were killed 72 h after ischemia. Oral pioglitazone (40 mg/kg/day, as a suspension in 0.5% carboxymethylcellulose) was administered to mice twice daily for 3 days before ischemia and twice daily after ischemia until the animals were killed. We investigated gelatinase activity by zymography and laminin immunohistochemistry. Histological analysis was also performed to test the protective effect of pioglitazone on neuronal damage. Mice treated with pioglitazone had attenuated gelatinase activity. Gelatin gel and in situ zymography showed up-regulation of gelatinase activity after ischemia. Pioglitazone significantly inhibited ischemia-induced elevation of the active form of MMP-9. Pioglitazone also reduced up-regulation of in situ gelatinase activity and laminin breakdown induced by ischemia in the hippocampus. There was marked neuronal damage in the CA1 and CA2 areas after ischemia. Neuronal damage in mice was significantly decreased by pioglitazone treatment, compared with vehicle-treated mice. Pioglitazone also inhibited TdT-mediated dUTP nick end labeling staining in CA1 and CA2 areas. Pioglitazone, a PPARgamma agonist, reduces delayed neuronal damage induced by global ischemia through inhibition of MMP-9 activity.
机译：先前的研究表明吡格列酮是一种过氧化物酶体增殖物激活的受体伽玛（PPARgamma）激动剂，可抑制包括神经组织在内的各种组织的缺血性损伤。吡格列酮还被证明可以降低基质金属蛋白酶（MMP）的活性。因为已知MMP在脑缺血的病理生理中起主要作用，所以本研究旨在测试吡格列酮是否通过MMP抑制来减轻缺血性神经元损伤。将C57BL / 6小鼠进行全脑缺血20分钟。缺血72小时后处死动物。在缺血前3天每天两次向小鼠施用口服吡格列酮（40mg / kg /天，作为在0.5％羧甲基纤维素中的悬浮液），在缺血后每天两次，直至杀死动物。我们通过酶谱和层粘连蛋白免疫组化研究明胶酶活性。还进行了组织学分析以测试吡格列酮对神经元损伤的保护作用。用吡格列酮治疗的小鼠的明胶酶活性减弱。明胶和原位酶谱显示缺血后明胶酶活性上调。吡格列酮显着抑制缺血诱导的MMP-9活性形式的升高。吡格列酮还减少了海马缺血引起的原位明胶酶活性和层粘连蛋白分解的上调。缺血后CA1和CA2区出现明显的神经元损伤。与载体治疗的小鼠相比，吡格列酮治疗显着降低了小鼠的神经元损伤。吡格列酮还抑制CA1和CA2区域中TdT介导的dUTP缺口末端标记染色。吡格列酮是一种PPARgamma激动剂，可通过抑制MMP-9活性来减轻由整体缺血引起的延迟神经元损伤。

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