慢性不可预知应激诱导的抑郁大鼠血清中神经递质含量的动态变化

目的观察慢性不可预知应激(CUS)并配合孤养诱导模型大鼠抑郁样行为过程中神经递质水平的变化,探讨神经递质作为诊断抑郁症的客观、可量化标志物的可能性。方法 利用CUS并配合孤养模型建立抑郁大鼠动物模型,以体质量、糖水偏爱率和旷场实验(穿格数和直立次数等)结果评定大鼠行为学的动态变化;采用高效液相-荧光法(HPLC-FD)测定血清中5-羟色胺(5-HT)、去甲肾上腺素(NE)、肾上腺素(E)、多巴胺(DA)、左旋多巴(L-DOPA)、5-羟基吲哚乙酸(5-HIAA)、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)、酪氨酸(Tyr)和色氨酸(Trp)等10种神经递质的含量;应用SPSS软件对体质量、糖水偏爱率和旷场数据等行为结果进行主成分分析,并采用回归分析方法分析行为学与神经递质变化间的相关性。结果 ①与正常对照组相比,造模期间第14天,模型组直立次数显著降低(P<0.05);造模期间第22天,模型组体质量、糖水偏爱率、穿格数和直立次数均显著降低(P<0.05)。②与正常对照组相比,造模期间第6天,模型组Tyr和5-HIAA的含量显著降低(P<0.05);造模期间第9天,NE的含量显著降低(P<0.05);造模期间第22天,NE和5-HT的含量显著降低(P<0.05);造模期间第15和22天,NE,5-HIAA,HVA和5-HT的含量显著降低(P<0.05)。③NE,HVA和5-HT的变化趋势为降低的程度逐渐增大,与行为学结果变化趋势接近;而Tyr的变化趋势为先升后降,5-HIAA,L-DOPA,DA,DOPAC,Trp和E呈波动性变化。主成分分析结果显示,第一主成分可代表93.47%的信息,结果可靠;相关性分析结果表明,5-HT,NE和HVA与第一主成分的相关性好。结论 血清中神经递质在CUS诱导抑郁样行为过程中呈动态变化,其中NE,5-HT和HVA的变化可以在一定程度上反映大鼠的抑郁状态和程度,可作为诊断抑郁症的临床辅助指标。

Change of serum neurotransmitter level in depression rats induced by chronic unpredictable stress

OBJECTIVE To observe the change of serum neurotransmitters in depression rats induced by chronic unpredictable stress (CUS) and to investigate the possibility of serum neurotransmitters being used a quantitative diagnostic biomarkers for depression. METHODS Depression was induced by CUS. Sucrose preference test and open-field test were applied to evaluate the behavior of CUS rats. The content of 5-hydroxytryptamine(5-HT), norepinephrine(NE), epinephrine(E), dopamine(DA), levodopa(L-DOPA), 5-hydroxy-indole-3-acetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), tyrosine(Tyr) and tryptophan(Trp) in serum was determined by reverse phase high performance liquid chromatography with fluorescence detector. RESULTS 1 Compared with normal control group, the body mass, preference sucrose, ambulation number and rearing number in CUS model rats showed a significant decrease after 21 d of stress exposure. 2 Compared with normal control group, the Tyr and 5-HIAA levels was significantly lower in CUS model rats on the 6th day, NE level was significantly lower in CUS rats on the 9th day, NE and 5-HT levels was significantly lower in CUS rats on the 12th day, levels of NE, 5-HIAA, HVA and 5-HT were significantly lower in CUS rats on the 15th and the 22nd day. 3 NE, HVA and 5-HT showed a tendency of gradual decline, while Tyr dropped after rise. 5-HIAA, L-DOPA, DA, DOPAC, Trp and E showed fluctuations. The principal compoent analysis showed that the first principal component could represent 93.47% of the information. Correlation analysis showed that 5-HT, NE and HVA were closely related to the first principal components. CONCLUSION During the development of rats' depression induced by CUS, the serum neurotransmitters change significantly. NE, 5-HT and HVA are possibly the biomarkers for auxiliary diagnosis of depression.