米氮平对睡眠剥夺小鼠学习记忆以及海马组织proBDNF、mBDNF表达的影响

Effects of mirtazapine on learning and memory function and expressions of proBDNF and mBDNF in hippocampus of mice with sleep deprivation

目的观察米氮平对睡眠剥夺小鼠学习记忆以及海马组织脑源性神经营养因子前体(proBDNF)和成熟体(mBDNF)表达的影响。方法 32只雄性小鼠随机均分为空白对照组(KB组)、模型对照组(MX组)、米氮平2.5mg/kg组(M1组)和米氮平10mg/kg组(M2组)。MX组、M1组和M2组小鼠灌胃16d后采用小平台水环境法建立24-h睡眠剥夺模型,采用Morris水迷宫实验观察小鼠学习记忆功能的变化。随后取海马组织测定其proBDNF和mBDNF含量。结果与KB组比较,MX组小鼠上台时间延长(P<0.01),穿越平台次数减少(P<0.05),海马proBDNF表达增加(P<0.01),mBDNF表达减少(P<0.01);与MX组比较,M2组小鼠上台时间缩短(P<0.05),穿越台次数增加(P<0.05),海马proBDNF表达减少(P<0.05),mBDNF表达增加(P<0.05)。结论米氮平能有效地减轻小鼠睡眠剥夺引起的学习记忆障碍,其作用可能与海马proBDNF表达降低和mBDNF表达增加有关。

Objective To observe the effects of mirtazapine on learning and memory function and the expressions of precursor brain-derived neurotrophic factor（proBDNF） and mature brain- derived neurotrophic factor（mBDNF） in the hippocampus in mice with sleep deprivation. Methods Thirty-two male mice were equally randomized into four groups of KB（normal saline infused per day without sleep deprivation）, MX （normal saline infused per day before sleep deprivation）, M1 （mirtazapine 2.5 mg/kg infused per day before sleep deprivation） and M2 （mirtazapine 10 mg/kg infused per day before sleep deprivation）. After gastric gavage for 16 days, the mice were sleep deprived for 24 hours using the method of modified multiple platform. The changes of learning and memory function were observed using Morris test. Then the expressions of proBDNF and mBDNF in the hippocampus were detected by Western blot. Results Compared with group KB, the latency to platform was lengthened （P〈0. 01）, the number of crossing the plat was decreased （P〈0. 05）, the expression of proBDNF was increased （P〈0. 01 ） and the expression of mBDNF was decreased （P〈0. 01） in group MX. Compared with group MX, the latency to platform was shortened （P〈0. 05）, the number of crossing the platform was increased（P〈0. 05）, the expression of proBDNF was decreased （P〈0. 05） and the expression of mBDNF was increased（P〈0. 05） in group M2. Conclusion Mirtazapine can effectively attenuate the adverse effects of sleep deprivation on learning and memory function of mice, which may be associated with lower expression of proBDNF and higher expression of mBDNF.