脑卒中后抑郁模型大鼠脑单胺递质变化及中药颐脑解郁方的干预作用

Changes in brain monoamine neurotransmitters of rats with poststroke depression and the interventional effect of Chinese herb of Yinao Jieyu prescription

目的:观察脑卒中后抑郁模型大鼠脑内单胺递质的含量变化及补肾疏肝中药颐脑解郁方对脑卒中后抑郁的干预作用。方法:实验于2005-02/2006-01在北京中医药大学基础医学院科研中心实验室完成。取雄性Wistar大鼠40只,按随机数字表法分为5组,即正常组、脑卒中组、脑卒中后抑郁模型组、氟西汀组、颐脑解郁方组,每组8只。正常组不干预,脑卒中组仅进行脑卒中手术,术后常规喂养;脑卒中后抑郁模型组、氟西汀组、颐脑解郁方组均进行脑卒中后抑郁模型制备,先进行脑卒中手术,术后常规喂养7d后,给予21d的慢性应激。造模结束后第1天开始,脑卒中组、脑卒中后抑郁模型组灌胃蒸馏水;颐脑解郁方组灌胃颐脑解郁方,剂量为9.92g/(kg·d);氟西汀组灌胃盐酸氟西汀,按照成人用量的7倍计算大鼠用量为2.33mg/(kg·d),共灌胃6周。给药结束后处死大鼠,采用高效液相-电化学方法测定大脑前皮质、海马去甲肾上腺素、多巴胺、5-羟色胺含量。结果:40只大鼠全部进入结果分析,无脱失。①各组大鼠的行为学表现:造模成功后,与正常组比较,脑卒中后抑郁模型组、氟西汀组、颐脑解郁方组大鼠体质量增长缓慢,理毛次数显著减少,毛色无光泽,蔗糖水摄入量下降,活动减少。给药6周后,氟西汀组、颐脑解郁方组大鼠的抑郁症状均有所改善。②各组大鼠大脑左侧前皮质单胺递质含量比较:脑卒中后抑郁模型组大鼠大脑左侧前皮质的5-羟色胺、去甲肾上腺素含量显著低于正常组(P<0.05～0.01),氟西汀组、颐脑解郁方组5-羟色胺、去甲肾上腺素含量显著高于脑卒中后抑郁模型组(P<0.05～0.01)。③各组大鼠大脑左侧海马单胺递质含量比较:脑卒中后抑郁模型组大鼠大脑左侧海马5-羟色胺、去甲肾上腺素和多巴胺含量显著低于正常组(P<0.05～0.01);颐脑解郁方组5-羟色胺、多巴胺、去甲肾上腺素含量高于脑卒中后抑郁模型组(P<0.05);氟西汀组5-羟色胺含量高于脑卒中后抑郁模型组(P<0.05)。结论:脑卒中后抑郁模型大鼠存在脑内单胺神经递质含量的减少,中药颐脑解郁方可增加中枢5-羟色胺、去甲肾上腺素及多巴胺的含量,疗效与盐酸氟西汀相近。

AIM： To observe the changes in brain monoamine neurotransmitters of rats with post stroke depression （PSD） and investigate, the interventional effects of Chinese herb of Yinao Jieyu prescription on PSD. METHODS： The experiment was conducted in the Central Laboratory of Science and Technology, College of Basic Medicine of Beijing University of Chinese Medicine from February 2005 to January 2006. Forty male Wistar rats were randomly divided into 5 groups： Normal group, stroke group, PSD model group, fluoxetine group and Yinao Jieyu prescription group with 8 rats in each group. Rats in the normal group received no intervention. Rats in the stroke group were given stroke operation and normally fed postoperation. Rats in the PSD model group, fluoxetine group and Yinao Jieyu prescription group were established into PSD models： normally fed for 7 days after the stroke operation and then given chronic stress for 21 days. Rats in the stroke group and PSD model group were administration with gastric perfusion of distilled water from the 1^st day after the modeling. Rats in the Yinao Jieyu prescription group were administrated at 9.92 g/kg per day, and rats in the fluoxetine group were gastrieally perfused with fluoxetine at 7 times of adult dose： 2.33 mg/kg per day for 6 continuous weeks. Rats were executed after the administration, and the contents of norepinephrine （NE）, dopamine （DA）, 5-hydroxytryptamine （5-HT） and its metabolite 5-hydroxyindoleacetic acid （5-HIAA） in anterior cerebral cortex hippoeampus were determined with the high performance liquid phase-electrochemical method. RESULTS： All the 40 rats were involved in the analysis of results, and no one withdrew from the study. ① Ethology of rats in each group： Compared with the normal group, the body mass of rats increased slowly in the PSD model group, fluoxetine group and Yinao Jieyu prescription group, besides, the grooming times of rats were significantly decreased and hair were dark, and the intake of cane sugar water decreased with less aetivites. Six weeks after administration, the depressive symptoms of rats were improved in the fluoxetine group and Yinao Jieyu prescription group. ② Comparison in monoamine neurotransmitters content of left cortex among all groups： The levels of 5-HT and NE in the PSD model group were significantly lower than those in the normal group （P 〈 0.05-0.01）, and those in the fluoxetine group and Yinao Jieyu prescription group were significantly higher than those in the PSD model group （P〈 0.05-0.01）. ③ Comparison in monoamine neurotransmitters in the hippocampus of rats among all groups： The levels of 5-HT, DA and NE in the left hippocampus of rats in the PSD model group were remarkably lower than those in the normal group （P 〈 0.05-0.01）, and those in the Yinao Jieyu prescription group were higher than those in the PSD model group （P 〈0.05）. The content of 5- HT in the fluoxetine group was higher than that in the PSD model group （P 〈 0.05）. CONCLUSION： The content of brain monoamine neurotransmitters decreases in rats with PSD, while Chinese herb Yinao Jieyu prescription can increase the level of 5-HT, NE and DA, the effect of which is similar to that of fluoxetine.