N-乙酰半胱氨酸对抑郁模型大鼠行为及神经递质的影响

目的 观察 N-乙酰半胱氨酸（NAC）对抑郁模型大鼠行为、各脑区单胺递质的影响， 探讨 NAC 潜在的抗抑郁作用及机制。 方法 选取成年雄性 SD 大鼠 32 只， 随机分为模型组、氟西汀（FLX）组、NAC 组、对照组， 每组 8 只；前 3 组单笼孤养， 釆用连续 6 周慢性轻度不可预见性应激（CUS）的方法建立慢性抑郁大鼠模型， 并于第 3 周末至第 6 周末对 NAC 组和 FLX 组分别给予 NAC 和 FLX 灌胃， 模型组和对照组给予同体积生理盐水灌胃。 CUS 前、后及干预后以体质量测量、糖水消耗实验、旷场实验对大鼠行为进行评估； 以库仑阵列电化学高效液相色谱法测定各组大鼠前额叶（PFC）、纹状体（ST）、杏仁核（AM）和海马（HIP）单胺神经递质去甲肾上腺素（NE）、5-羟色胺（5-HT）、多巴胺（DA）水平。 结果 （1）干预后对照组、NAC 组、FLX 组较模型组大鼠体质量增加多、糖水消耗量多、水平运动距离长、直立次数多、粪便粒数少（均 P < 0.05）。（2）与对照组相比， 模型组大鼠前额叶、纹状体、杏仁核、海马等脑区单胺神经递质 NE、DA 和 5-HT 水平明显降低（均 P < 0.05）；与模型组相比， NAC 组、FLX 组前额叶、纹状体、杏仁核、海马等 NE、DA、5-HT 浓度显著升高（均 P < 0.05）。 结论 NAC 和 FLX 均可有效改善抑郁模型大鼠的抑郁行为， 并在总体上提高前额叶、纹状体、杏仁核、海马等脑区单胺神经递质的水平。

Effects of N-acetylcysteine on behavior and monoamine neurotransmitters in rats with chronic unpredictable stress

Objective To investigate effects of N-acetylcysteine (NAC) on changes of the behavior and the monoamine neurotransmitters in prefrontal cortex (PFC), striatum (ST), amygdala (AM) and hippocampus (HIP) in rat model of chronic unpredictable stress (CUS), and to explore the possible mechanisms related to the NAC. Methods Thirty- two male Sprague-Dawle (SD) rats were divided into CUS group, fluoxetine group (FLX), NAC group and control group (n=8 for each group). Rats in CUS group, NAC group and FLX group were all fed alone and received CUS for 6 weeks to establish CUS model. Rats in NAC group and FLX group were given NAC and FLX by daily intragastric administration respectively during the last 3 weeks, while rats in CUS group and control group were given the same volume of solvent. Behavioral assessment including weight measurement, sucrose water consumption test, and opened field test were used for evaluation before and after CUS, and before and after intervention. The concentrations of the monoamine neurotransmitters (NE, DA, 5-HT) in PFC, ST, AM and HIP were measured with Coul array HPLC. Results (1) There were more increases in weight gain, sucrose consumption, and distance of horizontal moving and number of up-right, while the number of feces was less, after intervention in control group, NAC group and FLX group than those of CUS group (P < 0.05). (2) Neurotransmitters including NE, DA and 5-HT were significantly decreased in PFC, ST, AM and HIP in CUS group compared with that of control group (P < 0.05). The monoamine neurotransmitter (NE, DA and 5-HT) were significantly increased in the brain region (PFC, ST, AM and HIP) in NAC group and FLX group than those of CUS group (P < 0.05). Conclusion NAC and fluoxetine can effectively improve the depressive behavior of the CUS rats, increase the contents of monoamine neurotransmitters including NE, DA and 5-HT in PFC, AM, ST and HIP brain regions.