虾青素对缺氧缺血性脑损伤新生大鼠模型的神经保护作用

The neuroprotective effect of astaxanthin on newborn rat models of hypoxic-ischemic brain damage

背景:研究发现虾青素有良好的神经保护作用,但是对于其在新生儿缺氧缺血性损伤中的治疗作用,目前尚无相关报道。目的:构建缺氧缺血性脑损伤新生大鼠模型,观察虾青素对其产生的神经保护作用及作用的途径。方法:从98只7 d龄的SD乳鼠中随机取30只作为假手术组,其余大鼠结扎左颈总动脉2 h后,置于体积分数92%的特种标准气体、8%的氧气缺氧舱2 h建立缺血缺氧性脑损伤模型。假手术组仅分离颈总动脉,不予缺血缺氧处理。将造模成功的大鼠随机分为脑缺血缺氧组和虾青素治疗组,各30只。虾青素治疗组大鼠在脑缺血缺氧模型建成后立即通过腹腔注射80 mg/kg虾青素。结果与结论:与假手术组相比,脑缺血缺氧组大鼠缺血损伤区顶叶皮质中p-Akt、p-GSK3β、cleaved-caspase3蛋白的表达水平显著增加,Bcl-2蛋白的表达水平显著减少(P<0.05);与脑缺血缺氧组相比,虾青素治疗可以显著减少凋亡相关蛋白cleaved-caspase3蛋白的表达水平(P<0.05),显著上调Bcl-2蛋白的表达水平(P<0.05),明显减少凋亡细胞的数量(P<0.05)。提示虾青素可以显著改善新生大鼠缺氧缺血性脑损伤的预后及作用途径与上调Akt/GSK3β信号通路相关。

BACKGROUND： Several studies have demonstrated that astaxanthin has a good neuroprotective effect; however, the treatment effects of astaxanthin on newborns with hypoxic-ischemic brain damage have not been reported. OBJECTIVE： To build newborn rat models of hypoxic-ischemic brain damage, and investigate the neuroprotective effects of astaxanthin and the ways of action. METHODS： Thirty newborn Sprague-Dawley rats aged 7 days out of 98 were randomly taken as sham-operated group. The rest of rats were subjected to ligature of the left carotid artery for 2 hours and then placed in the hypoxic box containing 92% special standard gas and 8% oxygen to establish the models of hypoxic-ischemic brain damage. The rats in the sham-operated group only underwent separation of the carotid arteries, without hypoxic-ischemic treatment. Rat models of hypoxic-ischemic brain damage were randomly divided into hypoxic-ischemic brain damage and astaxanthin-treated groups, with 30 rats in each group. The rats in the astaxanthin-treated group were intraperitionally injected with 80 mg/kg astaxanthin after hypoxic-ischemic brain damage. RESULTS AND CONLUSION： Compared with the sham-operated group, the expression levels of p-Akt, p-GSK3β and cleaved-caspase-3 protein in the parietal cortex of ischemic damage area of rats were significantly increased, whereas Bcl-2 protein expression was significantly decreased in the hypoxic-ischemic brain damage group（all P〈0.05）. Compared with the hypoxic-ischemic brain damage group, astaxanthin treatment significantly reduced the expression level of apoptosis-related protein cleaved-caspase 3 protein（P〈0.05）, significantly increased the expression level of Bcl-2 protein（P〈0.05）, and significantly reduced the number of apoptotic cells in the hypoxic-ischemic brain area（P〈0.05）. These findings suggest that astaxanthin can distinctly improve the prognosis and ways of action of hypoxic-ischemic brain damage in newborn rats which associates with up-regulation of Akt/GSK3β signaling pathways.