摘要
目的观察解郁安神中药对慢性不可预见性应激(CUS)抑郁大鼠模型神经递质及脑源性神经营养因子(BDNF)的影响,探讨其抗抑郁的作用机制。方法雄性SD大鼠随机分为正常组,模型组,解郁安神中药小、中、大剂量组(8.2、16.3、32.7 g/kg),盐酸氟西汀组(10 mg/kg)。应激刺激开始的同时连续灌胃药物35 d。通过敞箱实验、新奇抑制摄食实验观察药物对大鼠行为学的影响;采用HPLC法测定药物对大鼠海马、皮层的多巴胺(DA)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)、去甲肾上腺素(NE)含量的影响;利用Western blot观察药物对大鼠海马BNDF的表达。结果模型组大鼠体重增长缓慢,在行为学测试中表现出自主活动减少;皮层的5-HT和NE的含量明显降低(P<0.05),海马5-HT及5-HIAA、NE的水平亦显著降低(P<0.05),BDNF的表达显著下降(P<0.05)。与模型组比较,解郁安神中药各剂量均可不同程度改善CUS抑郁大鼠自发活动的减少;中药中、大剂量及盐酸氟西汀可显著提高皮层5-HT、NE的含量(P<0.05),中药小、大剂量组可显著提高海马NE的含量(P<0.05),中药各剂量可显著提高海马5-HT、5-HIAA的含量(P<0.05);中药大剂量及盐酸氟西汀可上调海马BDNF的表达(P<0.05)。结论解郁安神中药抗抑郁的作用机制可能与其对神经递质的影响及上调脑源性神经营养因子有关。
Objective To observe the effect of TCM compound of resolving stagnation for tranquilization （ RST） on neurotransmitters and brain derived neurotrophic factors （ BNDF ） in depression rat model induced by chronic unpredictable stress （ CUS） , and to reveal the mechanism of RST on the treatment of depression.Methods Altogether 60 male SD rats were randomly divided into normal group, model group, high-, mid-and low-dose RST groups at dosage of 8.2, 16.3, 32.7 g/kg, and fluoxetine group with dose of 10 mg/kg.The rats of four therapy groups were administered intragastrically drugs with undergoing CUS for consecutive thirty-five days.The behavioral changes of rats were observed by open field test and novelty-suppressed feeding-test.The content of dopamine （ DA） , 5-hydroxeytryptamine（5-HT） , 5-hydroxyindole acetic acid （5-HIAA） and norepi-nephrine（ NE） in hippocampus and cortex were determined by HPLC.And the expression of BDNF in hippocampus was measured by Western blot.Results Compared with the normal group, the rats ’ weight increased slowlier and the spontaneous activity decreased in model group; the contents of 5-HT and NE in cortex and the content of 5-HT, 5-HIAA and NE in hippocampus significantly reduced （ P〈0.05 ）.Compared with the model group, the spontaneous activity significantly increased in all therapy groups;the contents of 5-HT and NE in cortex dramatically increased in fluoxetine group and mid-, high-dose group （ P〈0.05 ）;the contents of 5-HT and 5-HIAA in hippocampus significantly increased in all three RST groups （ P〈0.05 ）; the content of NE in hippocampus significantly increased in low-and high-dose group （ P〈0.05 ）.The expression of BDNF in hippocampus significantly increased in fluoxetine group and high-dose RST group （ P〈0.05）.Conclusion The anti-depression mechanism of TCM compound formulated by principle of resolving stagnation for tranquilization may be related to the effects of increasing neurotransmitters and up-regulation of BDNF.
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2015年第9期611-618,共8页
Journal of Beijing University of Traditional Chinese Medicine
基金
北京市教委基金资助项目(No.KM201310025013)
北京市属高等学校高层次人才引进与培养计划-长城学者项目资助(No.CIT&TCD20140329)
关键词
解郁安神
慢性不可预见性应激抑郁模型
神经递质
脑源性神经营养因子
大鼠
relieving stagnation and tranquilizing
chronic unpredictable stress （ CUS ）
neurotransmit-ters
brain derived neurotrophic factor（BDNF）
rats
