阿米替林对小鼠抑郁样行为的作用机制研究

Effect and mechanism of amitriptyline on depression-like behaviors in mice

目的研究阿米替林对小鼠抑郁样行为的影响及机制。方法用慢性束缚刺激建立抑郁模型,造模时间共3周。按照体重将ICR小鼠随机分为3组:正常组、模型组及实验组,每组12只。实验组小鼠腹腔注射给予阿米替林10μg·g^(-1),正常组和模型组分别给予蒸馏水。在造模持续2周后开始给药,连续给药1周。用旷场实验和强迫游泳实验检测小鼠抑郁样行为;用蛋白质印迹法检测小鼠海马脑源性神经营养因子(BDNF)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)蛋白表达(灰度值);用酶联免疫吸附法检测小鼠血清中促肾上腺皮质激素(ACTH)和皮质醇(CORT)的含量。结果正常组、模型组和实验组小鼠的中央区域活动路程的百分比分别为(13.05±1.69)%,(6.48±0.56)%和(11.50±1.33)%;这3组小鼠的不动时间百分比分别为(9.28±1.82)%,(16.43±1.61)%和(9.84±2.55)%;这3组的BDNF蛋白相对表达量分别为1.00±0.06,0.62±0.04和1.20±0.05;这3组的IL-1β蛋白相对表达量分别为1.00±0.04,1.32±0.06和0.89±0.06;这3组的TNF-α蛋白相对表达量分别为1.01±0.03,1.61±0.10和1.20±0.06;这3组的ACTH含量分别为(10.51±0.67),(17.20±0.61)和(13.72±0.86)mmol·L^(-1);这3组的CORT含量分别为(11.51±0.54),(17.53±0.31)和(16.39±0.36)mmol·L^(-1)。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.05);实验组与模型组比较,除CORT外差异均有统计学意义(均P<0.05)。结论阿米替林可缓解小鼠抑郁样行为,作用机制可能与降低ACTH水平和降低海马抗炎及外周抗炎相关。

Objective To study the effect and mechanisms of amitriptyline on depression-like behaviors in mice.Methods The model was established by chronic restraint stress,for three weeks.The ICR mice were randomly divided into three groups according to weight:Normal group,model group and experimental group,with 12 mice in each group.The mice in experimental group were given amitriptyline(10μg·g^(-1))and the mice in normal group and model group were given distilled water by intraperitoneal injection respectively.All the mice were given by administration for one week.The drug was given after 2 weeks of modeling.The behaviors of mice were detected by open field test and forced swimming test.The protein expression of brain derived neurotrophic factor(BDNF),interleukin-1β(IL-1β)and tumor necrosis factorα(TNF-α)in hippocampus of mice were detected by Western blot(gray value).The levels of adrenocorticotropic hormone(ACTH)and cortisol(CORT)in serum of mice were detected by enzyme linked immunosorbent assay.Results The percentage of distance moved in center in normal group,model group and experimental group were(13.05±1.69)%,(6.48±0.56)%and(11.50±1.33)%,respectively;the percentage of immobility duration were(9.28±1.82)%,(16.43±1.61)%and(9.84±2.55)%,respectively;the protein expression of BDNF in the three groups were 1.00±0.06,0.62±0.04 and 1.20±0.05,respectively;the protein expression of IL-1βin the three groups were 1.00±0.04,1.32±0.06 and 0.89±0.06,respectively;the protein expression of TNF-αin the three groups were 1.01±0.03,1.61±0.10 and 1.20±0.06,respectively;the levels of ACTH in serum in the three groups were(10.51±0.67),(17.20±0.61)and(13.72±0.86)mmol·L^(-1),respectively;the levels of CORT were(11.51±0.54),(17.53±0.31)and(16.39±0.36)mmol·L^(-1),respectively.Comparison between model group and normal group,the difference of indicators were significant(all P<0.05);comparison between experimental group and model group except the levels of CORT,the difference of indicators were significant(all P<0.05).Conclusion Amitriptyline can relieve the depression-like behaviors of mice,the mechanisms about that are in relation to decreasing the level of ACTH and inhibiting inflammation of the hippocampus and the peripheral circulation system.