虾青素提高血管性痴呆小鼠学习记忆能力

Improvement of astaxanthin on learning and memory ability of vascular dementia mice

目的探讨腹腔给药虾青素对于血管性痴呆(VaD)小鼠学习记忆能力的影响及其作用机制。方法采用双侧颈总动脉夹闭法建立小鼠VaD模型后随机分成假手术组、模型组、虾青素低剂量组及虾青素高剂量组,分别给予相应形式的药物治疗。Morris水迷宫观察各组小鼠的学习记忆及空间探索能力,尼氏染色、免疫组织化学染色、Western blotting及ELISA检测小鼠脑神经元的病理形态、脑内β-淀粉样肽42(Aβ_(42))蛋白表达及炎症相关因子白细胞介素(IL)-4及IL-6含量。结果模型组小鼠第4天及第5天的平均逃避潜伏期较假手术组显著增加(P<0.05),平台穿越次数及停留时间显著下降(P<0.05);尼氏染色显示,模型组小鼠海马区神经元固缩,排列紊乱,神经元数量较假手术组明显减少;经过不同剂量虾青素治疗干预后,小鼠的第4天和第5天平均逃避潜伏期较模型组显著下降(P<0.05),平台穿越次数及停留时间显著延长(P<0.05),神经元排列层次分明,尼氏染色阳性细胞较模型组明显增加,效果呈剂量依赖性。另外,免疫组织化学染色、Western blotting及ELISA检测显示,不同剂量虾青素干预组较模型组脑内Aβ_(42)蛋白及IL-6含量显著下降(P<0.05),IL-4含量显著增加(P<0.05)。结论虾青素能够降低脑内神经毒性蛋白Aβ_(42)的表达以及抑制脑内炎症反应,从而发挥神经元保护作用,改善小鼠的学习记忆能力。

Objective To study the effect and mechanism of astaxanthin on learning and memory ability of vascular dementia(VaD)mice.Methods The mice were used to establish VaD model by occlusion of bilateral common carotid artery.The mice were randomly divided into sham group,model group,astaxanthin low-dose group and astaxanthin high-dose group and then given corresponding forms of drug treatments.Morris water maze was used to investigate the learning,memory and space exploration abilities of mice in each group.At the same time,the pathological morphology of brain neurons,the expression of amyloid beta-peptides 42(Aβ_(42)) protein in brain and the content of interleukin(IL)-4 and IL-6 were respectively examined by Nissl staining,immunohistochemical staining,Western blotting and ELISA.Results The average escape latency of mice in the model group on the 4 th and 5 th days was significantly higher than sham-operated group(P<0.05),and the number of plateau crossings and the duration of stay decreased significantly(P<0.05).At the same time,Nissl staining showed that the neurons in the hippocampus of the model group were shrinking and disordered.The number of neurons in the model group was significantly reduced compared with the sham-operated group.The average escape latency of mice treated with different doses of astaxanthin on the 4 th and 5 th day was significantly lower than the model group(P<0.05).The number and duration of platform crossing were significantly longer than model group(P<0.05).The number of neurons in the intervention group was obviously higher than model group,and the effect was dose-dependent.In addition,immunohistochemical staining,Western blotting analysis and ELISA detection showed that the levels of Aβ_(42) protein and IL-6 in the astaxanthin intervention group decreased significantly compared with the model group(P<0.05),while the levels of IL-4 increased significantly(P<0.05).Conclusion Astaxanthin can reduce the expression of neurotoxic protein Aβ_(42) protein and inhibit the inflammatory response in the brain,which can protect neurons and improve the learning and memory ability of mice.