老年鼠海马自由基与学习记忆关系的研究

Relationship between learning ability and memory and free radical in hippocampus of old rats

目的 探讨老年鼠海马自由基与学习记忆的关系。方法 测试 116只雄性Sprague Dawley大鼠在水迷宫中的学习记忆成绩 ,其中老年鼠 4 6只、青年鼠 36只和成年鼠 34只 ,大鼠海马透析测定各组海马中的羟自由基和超氧化物歧化酶 (SOD)的含量 ,进行海马CA1和CA4段形态学检查 ,探讨自由基对海马细胞和学习记忆的影响。结果 老年鼠海马SOD活性 (U·g-1·min-1)为 4 10± 5 0 ,青年鼠为 880± 6 2 ,成年鼠为 86 0± 6 0。老年鼠比青年鼠和成年鼠海马自由基显著增加 (P <0 0 0 1) ,老年鼠海马细胞数目比对照组显著减少 (P <0 0 0 1) ,导致学习记忆成绩下降 (P <0 0 1)。结论老年鼠学习记忆能力的下降与自由基显著增加和海马神经元数量下降成正相关。

Objective To study the relationship between the amount of free radical in hippocampus and the learning ability and memory in old rats. Methods Morris water maze was used for 10 days to examine the learning scores, latency scores, and the loci of movement in the maze among 46 old rats (aged 20 months), 36 young rats (aged 6 months), and 34 adult rats (aged 12 months). Salicylate was injected intraperitoneally and hippocampus dialysis was performed. Chromatography was used to measure the basic values of 2,3DHBA and 2,5DHBA in dialysis fluid chemiluminometry was used to measure the superoxide dismutrase (SOD) in the sample. The rats were killed and their brains were taken out. Histological examination was conducted to calculate the number of neurons in CA1, CA4, and PM regions in hippocampus. Results The learning scores on the first, fifth, and tenth days were 36.5±5.9 sec, 38.6±5.9 sec, and 39.4±6.9 sec ( P >0.05) in the old rats; 60.2 ±5.4 sec, 156.8±5.8 sec, and 165.1±6.8 sec in the young rats; and 61.7±5.8 sec, 152.3±6.9 sec, and 168.7±6.5 sec in adult rats. The learning scores at any time point of old rats were significantly lower than those of the young and adults rats (all P <0.01). The latency scores of the first, fifth, and tenth days were 25.7±1.2 sec, 27.5±1.9 sec, and 27.7±1.9 sec in the old rats without significant difference between any two of these values ( P >0.05), however, the 3 latency scores of the old rats were all significantly larger than those of the young and adult rats (21.8±1.7 sec, 5.9±1.0 sec, and 3.6±0.6 sec, and 21.8±1.6 sec, 5.0±0.9 sec, and 4 8±0.7 sec respectively, all P <0.01). The basic value of 2,3DHBA after intraperitoneal injection of salicylate was 20.7±0.3 pmol/ml in the old rats, 5 times that of the young rats and 6 times that of the adult rats ( P <0.01). The basic value of 2,5DHBA after intraperitoneal injection of salicylate was 60.12 pmol/ml in the old rats, 6 times that of the young rats and 5.8 times that of the adult rats ( P <0.01). The SOD activity was 410 U· g -1 · min -1 ± 50 U · g -1 · min -1 , significantly lower than those in the young and adult rats (880 U ·g -1 ·min -1 ± 62 U ·g -1 · min -1 and 860 U ·g -1 · min -1 ± 60 U · g -1 · min -1 (both P <0.01). The values of neuron density in CA1, CA4, and PM regions of the old rats were all significantly lower than those of the young and adult rats (all P <0.01). Conclusion The decrease of learning ability in old rat is positively correlated with the increase of free radicals and loss of neurons in hippocampus.