Department of Neurology and Stroke Center, Tokyo General Hospital, 3-15-2 Ekoda Nakano-ku, Tokyo 165-8906, Japan; Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Life Sci. 2017 Jan 1;168:7-15. doi: 10.1016/j.lfs.2016.11.004. Epub 2016 Nov 5.
Rats subjected to transient focal ischemia and cultured neuronal cells subjected to oxygen-glucose deprivation (OGD) were treated with clarithromycin (CAM) to evaluate the effects of CAM in protecting against neuronal damage.
Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90min and then reperfused. Each animal was given an oral dose clarithromycin (CAM, 100mg/kg) or vehicle alone just after the ischemia was commenced. The infarct volume, edema index and neurological performance were assessed after 24 and 72h of reperfusion. The cerebral blood flow (CBF) was measured with an MRI system at 90min after MCAO. After 24 and 72h, oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) were assessed by immunohistochemical analyses and degenerative cells were assessed in the cortex by Fluoro-Jade C (FJC) labeling. The cultured neuronal cells were also used to examine the effects of CAM exposure on the viability of the cells after OGD.
CBF was unchanged between the two groups. Significant reductions of the infarct volume and edema index, an improved neurological deficit score, a significant suppression of 4-HNE and 8-OHdG expression, marked reductions of Iba-1 and TNF-α expression, and a significant reduction of FJC-positive cells were also observed in the CAM-treated animals at both time points. Treatment with 10μM and 100μM CAM in vitro significantly reduced cell death after OGD.
CAM appears to provide antioxidant and anti-inflammatory effects and protect against neuronal damage after cerebral ischemia and OGD.
对短暂性局灶性脑缺血的大鼠和氧葡萄糖剥夺（OGD）培养的神经元细胞进行克拉霉素（CAM）治疗，以评估 CAM 对神经元损伤保护作用。
将 Sprague-Dawley 大鼠进行大脑中动脉闭塞（MCAO）90 分钟，然后再灌注。每个动物在缺血开始后立即给予口服克拉霉素（CAM，100mg/kg）或单独给予载体。在再灌注 24 和 72 小时后评估梗死体积、水肿指数和神经功能表现。在 MCAO 后 90 分钟使用 MRI 系统测量脑血流（CBF）。在 24 和 72 小时后，通过免疫组织化学分析评估氧化应激（4-HNE、8-OHdG）和炎症（Iba-1、TNF-α），并通过 Fluoro-Jade C（FJC）标记评估皮质中的变性细胞。还使用培养的神经元细胞来检查 CAM 暴露对 OGD 后细胞活力的影响。
两组之间 CBF 没有变化。在两个时间点，CAM 治疗的动物均观察到梗死体积和水肿指数显著减少、神经功能缺损评分改善、4-HNE 和 8-OHdG 表达显著抑制、Iba-1 和 TNF-α 表达明显减少以及 FJC 阳性细胞显著减少。体外用 10μM 和 100μM CAM 治疗显著降低 OGD 后细胞死亡。
CAM 似乎提供抗氧化和抗炎作用，并在脑缺血和 OGD 后保护神经元损伤。
