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Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells

机译:红霉素对培养神经元细胞缺氧缺糖后脑缺血再灌注损伤及细胞活力的神经保护作用

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This study aims to determine if erythromycin has neuroprotective effects against transient ischemia and oxygen-glucose deprivation (OGD) in cultured neuronal cells. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90min, followed by reperfusion. The animals received a subcutaneous single injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. Infarct volume, edema index, and neurological performance were evaluated at 24 and 72 h after reperfusion. Immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-alpha) were conducted in the cortex at 24 h. Primary cortical neuronal cell cultures were prepared from the cerebral cortices of the animals and then subjected to OGD for 3 h. Ten or 100 muM EM was added before OGD to determine the effect of EM on cell viability after OGD. EM significantly reduced infarct volume (p<0.01) and edema volume (p<0.05) and improved neurological deficit scores (p<0.05) at 24 and 72 h. EM significantly suppressed the accumulation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) and markedly reduced Iba-1 (p<0.01) and TNF-a expression (p<0.01). Treatment with 100 muM EM in vitro significantly reduced cell death after OGD. EM reduces neuronal damage following cerebral ischemia and OGD and may have antioxidant and anti-inflammatory effects.
机译:这项研究旨在确定红霉素对培养的神经元细胞是否具有针对短暂性缺血和氧葡萄糖剥夺(OGD)的神经保护作用。对Sprague-Dawley大鼠进行大脑中动脉闭塞90分钟,然后再灌注。缺血后立即给动物皮下单次注射乳酸红霉素(EM,50 mg / kg)或赋形剂。在再灌注后24和72小时评估梗塞体积,水肿指数和神经系统性能。在24小时的皮质中进行了氧化应激(4-HNE,8-OHdG)和炎症(Iba-1,TNF-α)的免疫组织化学分析。从动物的大脑皮层制备原代皮层神经元细胞培养物,然后进行OGD 3 h。在OGD之前添加10或100μMEM,以确定EM对OGD后细胞活力的影响。 EM在24和72 h显着降低了梗塞体积(p <0.01)和水肿体积(p <0.05),并改善了神经功能缺损评分(p <0.05)。 EM显着抑制了4-HNE(p <0.01)和8-OHdG(p <0.01)的积累,并显着降低了Iba-1(p <0.01)和TNF-a的表达(p <0.01)。体外用100μMEM处理可显着降低OGD后的细胞死亡。 EM减少了脑缺血和OGD后的神经元损害,并可能具有抗氧化和抗炎作用。

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