摘要
目的探讨二十二碳六烯酸（DHA）对新生SD大鼠缺氧缺血性脑损伤后远期学习记忆障碍的影响及其可能机制。方法将60只7d龄新生SD大鼠按随机数字表法分为假手术组、对照组和DHA组，每组20只。对照组和DHA组分离并结扎左侧颈总动脉2．5h后在8％氧浓度环境中缺氧处理2h，假手术组只分离左侧颈总动脉但不结扎、不进行缺氧处理。造模后DHA组腹腔注射15mg／kgDHA，假手术组及对照组腹腔注射等体积聚乙二醇4000，连续10d。造模后48h各组取10只大鼠处死取材，采用尼氏染色观察大鼠海马CA1区及纹状体边缘区病理形态变化，采用TUNEL染色检测细胞凋亡情况，采用免疫组化染色检测凋亡相关蛋白Bax、Caspase-3阳性细胞表达；各组剩余10只大鼠2月龄时采用Morris水迷宫实验检测学习记忆能力，采用免疫组化染色检测N-甲基-D-天冬氨酸（NMDA）受体I（NMDAR1）阳性细胞表达。结果与对照组比较，DHA组海马CAl区及纹状体边缘区病理形态均有明显改善，凋亡细胞数明显减少，Bax、Caspase．3阳性细胞表达明显减少，差异均有统计学意义（P〈0．05）。Morris水迷宫实验可见DHA组逃避潜伏期较对照组明显缩短，海马CA1区及纹状体边缘区NMDAR1阳性细胞表达较对照组明显增加，差异均有统计学意义（P〈0．05）。结论DHA有改善缺氧缺血性脑损伤所致远期学习记忆障碍的作用．其机制可能与早期抑制海马CA1区及纹状体边缘区的细胞凋亡及晚期上调NMDAR1的表达有关。
Objective To explore the effect of docosahexaenoic acid （DHA） on long-term learning and memory disorders and potential mechanism in rats after hypoxic ischemic brain damage. Methods Sixty neonatal 7-day-old SD rats were ramdonly divided into three groups： group S （sham operation＋vehicle treatment）, group C （hypoxic-ischemie brain damage [HIBD]＋vehicle treatment） and group D （HIBD＋DHA treatment）. After left common carotid artery was isolated and ligated for 2.5 h, rats of group C and group D were put into a condition which oxygen concentration was about 8% for 2 h; rats in the group S were only isolated the left carotid artery, without ligation or hypoxia treatment; rats in the group D were intraperitoneally injected DHA of 15 mg/kg after modeling, and rats in the group S and group C were intraperitoneally injected equivalent volume of vehcle, once a day for 10 consecutive days. The pathomorphology changes of the hypocampal CA1 area, and marginal division of striatum were observed by Nissl staining 48 h after modling; the apoptosis cells were measured by TUNEL; immunohistoehemical method was used to detect the expressions of Bax and Caspase-3 positive cells in the two brain areas. Morris water maza test was used to evaluate the long-term lerning and momory functions of 2-month-old rats, and the expressions of N-methyl-D-aspartate receptor 1 （NMDAR1）positive cells were detected by immunohistochemical method. Results The pathomorphology damage was significantly improved, the expressions of Bax and Caspase-3 positive cells and the neuron apoptosis in hypocampal CA1 areas and marginal division of striatum in group D were all signficantly decreased as compared with those in the group C （P〈0.05）. Rats in group D had significantly decreased escape latency as compared with those in group C in Morris water maze test （P〈0.05）, and the expression of NMDAR1 positive cells in the two brain areas of group D was significantly increased as compared with that in the group C （P〈0.05）. C
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2016年第7期678-684,共7页
Chinese Journal of Neuromedicine
基金
国家自然科学基金（81371514）
