孕烯醇酮对大鼠空间学习记忆能力和ChAT蛋白表达的影响

The effect of pregnenolone on the ability of learning and memory spatial and the expression of ChAT of rats

目的:研究孕烯醇酮(Pregnenolone,PREG)干预对老年雄性SD大鼠空间学习记忆能力的影响,探讨PREG的潜在神经保护作用及其机制。方法:24月龄雄性SD大鼠40只,随机分为对照组(A组)、溶剂对照组(B组)、低剂量PREG(0.5 mg/kg)干预组(C组)、高剂量PREG(2.0 mg/kg)干预组(D组),隔日腹腔注射一个月,利用Y迷宫训练评估PREG对实验大鼠空间学习记忆能力的影响,运用免疫荧光技术和Western Blot检测分析大鼠记忆相关脑区ChAT蛋白表达的变化。结果:Y迷宫训练结果显示D组大鼠平均连续正确反应次数为7.5±1.35,明显多于其他各组;免疫荧光检测结果显示D组大鼠前额叶、颞叶、海马内ChAT免疫阳性的细胞数量相应是26.8±2.6、19.8±2.6、25.8±2.4,明显多于其他处理组;Western Blot检测显示D组大鼠前额叶、颞叶、海马皮层组织ChAT蛋白的表达明显高于其他各组(P<0.05)。结论:PREG有助于改善老年雄性SD大鼠空间学习记忆能力,其作用机制可能是促进了大鼠记忆相关脑区ChAT的表达上调,提高了胆碱能神经元细胞的功能活性。

Objective： To observe the effect of pregnenolone（ PREG） intervention on the ability of spatial learning and memory of the aged male SD rats,and explore the potential neuroprotective mechanism of PREG. Methods： Forty 24-month-old male SD rats were randomly divided into four groups： control group（ group A）; solvent control group（ group B）; low-dose PREG（ 0. 5 mg / kg） intervention group（ group C）; high-dose PREG（ 2. 0 mg / kg） intervention group（ group D）. Rats in each group accordingly were intraperitoneal injected with equal dose of saline,DMSO,PREG（ 0. 5mg / kg）,PREG（ 2. 0 mg / kg） by every other day for one month. The spatial learning-memory ability of rats was evaluated by Y-maze training,and the expression of ChAT protein on the memory-related encephalic region was detected by immunofluorescence technique and Western Blot methods. Results： Y- maze training results showed that the average-consecutive-correct-responses frequency of group D was 7. 5 ± 1. 35,significantly more than the other groups; immunofluorescence analysis showed that the number of ChAT immunoreactive cells in the prefrontal lobe,temporal lobe,hippocampus of group D was 26. 8 ± 2. 6,19. 8 ± 2. 6,25. 8 ± 2. 4 corresponding,apparently more than other groups; Western Blot analysis showed that the expression of ChAT protein on the prefrontal lobe,temporal lobe,hippocampus of group D was significantly up-regulated than other groups（ P 〈 0. 05）. Conclusions： The results indicate that PREG could improve the ability of spatial learning and memory of the aged male SD rats,which may be achieved by promoting the expression of ChAT protein on the memory-related brain regions of rats and raising the functional activity of the cholinergic system neu-rons.