虾青素通过抗氧化作用改善血管性痴呆小鼠学习记忆能力

Astaxanthin Improves Learning and Memory Ability of Vascular Dementia Mice Through Antioxidant Effect

目的观察虾青素对血管性痴呆小鼠学习记忆能力的影响及作用机制。方法通过永久性结扎右侧颈总动脉建立血管性痴呆模型,造模成功后将模型小鼠随机分成模型对照组、虾青素组(50,100和200 mg·kg^-1),另设假手术组,分别灌胃给予相应剂量虾青素或者羧甲基纤维素溶液,每天1次连续给药1个月,药物干预结束后,应用Morris水迷宫检测小鼠学习记忆能力,强迫游泳实验用于检测小鼠抑郁情况,采用Nissl染色观察小鼠海马神经元形态变化,酶标仪检测各组小鼠海马中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,通过二氢乙锭(DHE)染色观察小鼠海马结构活性氧自由基(ROS)含量。结果永久性结扎右侧颈总动脉模型造成小鼠平均逃避潜伏期时间和水中静止不动时间与假手术组相比增长(P<0.05),且海马神经元排列紊乱,结构破坏严重,细胞周围间隙增大呈空泡样变。虾青素治疗干预组小鼠平均逃避潜伏期时间和水中静止不动时间较模型对照组显著降低(P<0.05),海马神经元细胞结构也有改善,且效果呈剂量依赖性,虾青素200 mg·kg^-1是3个剂量组中改善最明显的。模型对照组小鼠海马结构中SOD活力值较假手术组明显降低(P<0.05)、MDA含量显著上升及ROS的荧光强度相对假手术组变强,虾青素组(50,100和200 mg·kg^-13个剂量组)均提高海马结构中SOD活力值、降低MDA含量和ROS荧光强度,其中以虾青素组200 mg·kg^-1表现最明显,与模型对照组相比差异具有统计学意义。结论虾青素通过抗氧化作用改善血管性痴呆小鼠学习记忆能力,发挥保护神经元的作用,且成剂量依赖关系。

Objective The purpose of this study was to observe the effects and explore the underlining mechanisms of astaxanthin on the ability of learning and memory of vascular dementia mice.Methods Vascular dementia(VD)model was established by the permanent ligation of the rightcommon carotid artery.The mice were randomly divided into model control group,astaxanthin(50,100 and 200 mg·kg^-1)group.After the intervention,the ability of learning and memory was explored by Morris water maze test.Forced swimming test was used to detect the depression degree.Using the Nissl staining,the morphological changes of hippocampal neurons were observed.The contents of SOD and MDA were tested by microplate reader in the hippocampus;DHE staining method was used to observe ROS fluorescence intensity in the hippocampus of mice.Results The permanent ligation of right common carotid artery model could cause the average escape latency time and the immobility time longer than sham operation group.And hippocampal neurons hierarchy was unclear and the arrangements were disordered(P<0.05).Moreover,the cell structure was destroyed seriously,and the space around the cells was enlarged,showing vacuole like changes.Astaxanthin(50,100 and 200 mg·kg^-1)reduced the average escape latency time and the immobility time,and improved the hippocampus neuron structure.The astaxanthin 200 mg·kg^-1 group showed the best improvement among the three groups.Compared with model control group,the SOD activity significantly reduced,and MDA content and ROS fluorescence intensity increased in the hippocampus of model control group.Astaxanthin(50,100 and 200 mg·kg^-1)group increased SOD activity,decreased the MDA content and the ROS fluorescence intensity in the hippocampus,and the astaxanthin 200 mg·kg^-1 group also had the best effects which was similar to those of sham operation group.Conclusion Astaxanthin could improve the ability of learning and memory of vascular dementia mice by the antioxidant effect,and play a role in protecting neurons in a dose-dependent relationship.