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
OBJECTIVE To observe the change of serum neurotransmitters in depression rats in- duced by chronic unpredictable stress (CUS) and to investigate the possibility of serum neurotransmit- ters being used a quantitative diagnostic biomarkers for depression. METHODS Depression was in- duced 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 Com- pared 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.③NE, 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 compo nents. CONCLUSION During the development of rats' depression induced by CUS, the serum neuro- transmitters change significantly. NE, 5-HT and HVA are possibly the biomarkers for auxiliary diagnosis of depression.