Katayama Yasuo, Inaba Toshiki, Nito Chikako, Ueda Masayuki, Katsura Kenichiro
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan; Department of Neurology and Stroke Center, Tokyo General Hospital, 3-15-2 Ekoda, Nakano-ku, Tokyo 165-8906, Japan.
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Brain Res. 2014 Nov 7;1588:159-67. doi: 10.1016/j.brainres.2014.09.016. Epub 2014 Sep 28.
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 90 min, followed by reperfusion. The animals received a subcutaneous single injection of erythromycin lactobionate (EM, 50mg/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-α) were conducted in the cortex at 24h. Primary cortical neuronal cell cultures were prepared from the cerebral cortices of the animals and then subjected to OGD for 3h. Ten or 100 μM 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-α expression (p<0.01). Treatment with 100 μM 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.
本研究旨在确定红霉素对培养的神经元细胞短暂性缺血及氧-葡萄糖剥夺（OGD）是否具有神经保护作用。将Sprague-Dawley大鼠进行大脑中动脉闭塞90分钟，随后再灌注。动物在缺血后立即皮下单次注射乳糖酸红霉素（EM，50mg/kg）或赋形剂。在再灌注后24小时和72小时评估梗死体积、水肿指数和神经功能表现。在24小时时对皮质进行氧化应激（4-HNE、8-OHdG）和炎症（Iba-1、TNF-α）的免疫组织化学分析。从动物的大脑皮质制备原代皮质神经元细胞培养物，然后进行3小时的OGD。在OGD前加入10或100μM的EM，以确定EM对OGD后细胞活力的影响。EM在24小时和72小时时显著减小梗死体积（p<0.01）和水肿体积（p<0.05），并改善神经功能缺损评分（p<0.05）。EM显著抑制4-HNE（p<0.01）和8-OHdG（p<0.01）的积累，并显著降低Iba-1（p<0.01）和TNF-α表达（p<0.01）。体外使用100μM的EM处理可显著减少OGD后的细胞死亡。EM可减轻脑缺血和OGD后的神经元损伤，可能具有抗氧化和抗炎作用。
