芹菜素对缺血缺氧脑损伤大鼠早期认知功能的影响

目的:探讨芹菜素对新生大鼠缺血缺氧脑损伤后早期认知功能的影响。方法:根据改良Rice模型建立新生大鼠缺血缺氧脑损伤模型,随机分为假手术组(Sham-operated,SH)、模型组(Model,M)、芹菜素干预组(Apigenin,A)和神经节苷脂GM1有效对照组(Ganglioside-GM1,GM1)。各组按后期测试的日龄不同又分为21日龄组和31日龄组,分别在Morris水迷宫中进行测试,测试结束后处死留取脑组织标本观察大鼠脑组织结构改变。结果:1.脑组织病理观察,(1)肉眼观:29只缺血缺氧脑损伤大鼠脑组织呈现明显的脑萎缩改变,约占51.8%(29/56)。假手术组大鼠无脑组织萎缩。(2)光镜观察:SH组的神经元细胞丰富且排列整齐有序,间质均匀;M组可见明显的胶质细胞增生,神经元排列不规则;A组和GM1组神经元细胞排列欠规则,较多见胶质细胞。(3)尼氏小体定量-神经细胞活力分析:M组、A组GM1组较相应SH组活力下降,有显著性差异(P0.01或P0.05);31日龄组较21日龄组升高,各组均有显著性差异(P0.01)。(4)海马组织电镜观察:SH组神经细胞结构正常,突触前膜内少见线粒体,其余各组神经细胞有不同程度核固缩表现及内质网扩张等,海马突触内见较多线粒体。2.Morris水迷宫实验,(1)空间定位(平均逃避潜伏期):M21组潜伏期较SH21组明显延长,空间定位学习能力差(P0.01);A21组潜伏期较M21组缩短(P0.05);GM1组潜伏期与M组比较差异无统计学意义(P0.05);31日龄组潜伏期较相应21日龄组缩短,差异有统计学意义(P0.01或P0.05)。(2)空间记忆:平均穿台次数:A21组较GM1-21组多,有显著性差异(P0.05);GM1-31组较GM1-21多,有显著性差异(P0.05)。平均台周Ⅰ区时间:A31组较A21组长(P0.05)。平均台周Ⅰ区路程:GM1-31组较GM1-21组长(P0.01)、A31组较A21组长(P0.05)。结论芹菜素可改善新生期缺血缺氧脑损伤后21日龄大鼠的空间定位学习能力。

Effect of Apigenin on Early Cognition of Rats with Ischemic Hypoxia Neonatal Brain Damage

Objective:To investigate the effects of apigenin on early cognition of rats with ischemic hypoxia neonatal brain damage.Methods:On basis of the modified rat model,ninety Sprague-Dawley rats were randomized into 4 groups:sham-operated group(SH);model groups(M);apigenin-treated groups(A) and ganglioside-GM1 control groups(GM1).According test timing in the Morris water maze,each group was divided into two different age groups,21-day-old group and 31-day-old group.The rats were sacrificed after tests to obtain brain tissues for optic microscope and electromicroscope,and Nissl body quantitation-neurocyte activity analysis was made.Results:1.Brain pathology(1)Gross appearance:Obvious ischemic hemisphere atrophy was observed in 29 samples(29/56,51.8%) and no abnormality in SH group.(2)Cellular morphology under the microscope:Nissl stain of ischemic cortex showed obvious glial cells infiltration or hyperplasia,and neurons lined irregularly in group M and group A and group GM1.No changes in Group SH.(3)Nissl body quantitation-neurocyte activity analysis:Significant less activity in groups A21,M21and GM1-21 than group SH21(P<0.05,P<0.01).More activity in 31-day-old groups than in 21-day-old groups respectively(P<0.01).(4)The electromicroscope observation:the cell structures in SH group were normal in ischemic hippocampus.Karyopycnosis and dilated endoplasmic reticulum were found in another three groups.More mitochondria were found in the presynaptic membrane in ischemic hippocampus in group M、A and GM1 than in group SH.2.The Morris water maze ⑴The spatial localization learning:the average escaping latency of group M21 was remarkably longer than group SH21(P<0.01);the learning score of group A21 was much better than M21(P<0.05),there was no significant difference between GM1-21 and M21.31-day-old groups had higher scores than 21-day-old groups respectively(P<0.05,P<0.01).(2)The spatial memory:the average passing platform times in group A21 was much more than in GM1-21(P<0.05),and that in GM1-31 was significantly more than in group GM1-21(P<0.05);the averageⅠ region time in group A31 was more than in group A21(P<0.05);the averageⅠ region distance in group A31 was significantly more than in group A21(P<0.05),and that in group GM1-31 was significantly more than that in group GM1-21(P<0.01).Conclusions:Apigenin may improve the spatial localization learning potential in neonatal ischemic hypoxia brain damaged rats,especially in 21-day-old rats.