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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。
AIM: To investigate the effect of pregnenolone (PREG) intervention on spatial learning and memory in aged male Sprague-Dawley rats and to explore the potential neuroprotective effect of PREG and its mechanism. Methods: Forty male Sprague-Dawley rats of 24 months old were randomly divided into 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). The rats in group D were injected intraperitoneally for one month on the other day. The Y maze training was used to evaluate the effect of PREG on spatial learning and memory in experimental rats. Immunofluorescence and Western Blot were used to analyze the memory-related brain regions ChAT protein expression changes. Results: The results of Y maze training showed that the mean continuous correct reaction frequency in group D was 7.5 ± 1.35, which was significantly more than that in other groups. The result of immunofluorescence showed that ChAT immunoreactive cells in frontal lobe, temporal lobe and hippocampus in group D The numbers were 26.8 ± 2.6, 19.8 ± 2.6 and 25.8 ± 2.4, respectively, which were significantly higher than those of other groups. Western Blot showed that the expression of ChAT protein in prefrontal cortex, temporal lobe and hippocampus in D group was significantly higher than that in other groups P <0.05). CONCLUSION: PREG can improve spatial learning and memory in aged male SD rats. Its mechanism may be that the expression of ChAT is upregulated and the functional activity of cholinergic neurons is increased in rats.