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目的研究慢性睡眠剥夺(CSD)对大鼠学习记忆功能的损害以及对海马、下丘脑中多巴胺(DA)含量和D1受体表达量的影响。方法健康成年雄性SD大鼠经过筛选后随机分为CSD组、大平台铁丝网格实验对照(TC)组和空白对照(BC)组,每组10只。采用改良多平台睡眠剥夺法建立大鼠CSD模型,每天剥夺18 h,连续21 d。TC组除剥夺箱底为罩有铁丝网格的大平台外,其他环境与CSD组一致。利用Morris水迷宫和自主活动箱在CSD的第7、14、21天检测大鼠学习记忆功能的变化;CSD 21 d后分别应用高效液相-电化学(HPLC-ECD)法和蛋白质印迹法检测大鼠海马、下丘脑中DA含量和D1受体蛋白表达量的变化。结果与BC组和TC组相比,CSD组大鼠毛色无光泽、精神疲惫且易激惹,自CSD 3 d起,体质量在各时间点降低,差异有统计学意义(P<0.01)。CSD组大鼠与其他两组相比,逃逸潜伏期在各时间点延长,穿环数减少,差异有统计学意义(P<0.01);与其他两组相比,CSD组大鼠自主活动总路程缩短(P<0.05)、自主活动次数减少(P<0.01);HPLC-ECD及蛋白质印迹结果显示,CSD组大鼠与其他两组相比,海马及下丘脑中DA含量、D1受体蛋白表达均减少,差异有统计学意义(P<0.05)。TC组与BC组大鼠相比,学习记忆能力、各脑区DA含量和D1受体蛋白表达差异均无统计学意义。结论CSD可损害大鼠学习记忆功能,海马、下丘脑中DA含量和D1受体表达水平降低可能是其潜在机制之一。
Objective To investigate the effects of chronic sleep deprivation (CSD) on learning and memory in rats and the effects of chronic sleep deprivation (CSD) on dopamine (DA) and D1 receptor expression in the hippocampus and hypothalamus. Methods Healthy adult male Sprague-Dawley rats were randomly divided into CSD group, large platform barbed wire grid control (TC) group and blank control group (BC) with 10 rats in each group. The rat model of CSD was established by modified multi-platform sleep deprivation method, deprived of 18 h every day for 21 consecutive days. TC group in addition to stripping the bottom of the barbed wire grid with a large platform, the other environment consistent with the CSD group. The change of learning and memory function of rats was detected on the 7th, 14th and 21st days of CSD by Morris water maze and voluntary exercise box. After 21 days of CSD, HPLC-ECD and Western blotting were used respectively Changes of DA content and D1 receptor protein expression in rat hippocampus and hypothalamus. Results Compared with BC group and TC group, CSD rats were dull, fatigued and irritable. From the 3rd day of CSD, the body weight of rats in CSD group decreased at different time points, with significant difference (P <0.01). Compared with the other two groups, the escape latency in CSD group was prolonged at each time point, and the number of perforated rings was decreased, the difference was statistically significant (P <0.01). Compared with the other two groups, the total distance traveled by CSD group (P <0.05), and the number of spontaneous activities decreased (P <0.01). The results of HPLC-ECD and Western blotting showed that compared with the other two groups, the content of DA and the expression of D1 receptor in hippocampus and hypothalamus of rats in CSD group All decreased, the difference was statistically significant (P <0.05). There was no significant difference in learning and memory ability, DA content in each brain region and D1 receptor protein expression between TC group and BC group. Conclusion CSD can impair the learning and memory function of rats, and the decrease of DA and hippocampal hypothalamus may be one of its underlying mechanisms.