逍遥解郁方抗大鼠卒中后抑郁的相关作用机制研究

Mechanism of Xiaoyao Jieyu Recipe in treating post-stroke depression in rats

目的:基于单胺能神经信号通路探讨逍遥解郁方抗大鼠卒中后抑郁(PSD)的作用机制。方法:选取SD大鼠50只,随机分为空白组、模型组、氟西汀组及中药低、高剂量组,每组10只。首先采用大脑中动脉线栓阻塞法(MCAO)建立卒中大鼠模型,在此基础上采用慢性不可预见性温和刺激法(CUMS)结合孤养法建立抑郁模型。造模成功后,各药物组大鼠分别给予相应药物连续灌胃28 d。采用强迫游泳实验和糖水偏好实验对大鼠进行行为学评定;采用ELISA法检测血浆5-羟色胺(5-HT)和去甲肾上腺素(NE)浓度; RT-PCR法检测大鼠海马组织5-HT_(1A)R、5-HT_(2A)R mRNA表达。结果:与空白组比较,模型组大鼠在强迫游泳实验中不动时间明显延长、挣扎时间明显缩短,糖水偏好度明显降低(P<0.01);与模型组比较,氟西汀组大鼠不动时间无明显变化(P>0.05),中药干预各组大鼠不动时间明显缩短(P<0.01),各组大鼠挣扎时间均明显延长(P<0.01),且糖水偏好度明显增加(P<0.05)。与空白组比较,模型组大鼠血浆5-HT及NE含量均明显降低(P<0.01);与模型组比较,各药物组大鼠血浆5-HT及NE含量明显升高(P<0.05)。与空白组比较,模型组大鼠海马组织5-HT_(1A)R mRNA表达明显降低,5-HT_(2A)R mRNA表达明显增加(P<0.01);与模型组比较,各药物干预组大鼠海马组织5-HT_(1A)R mRNA表达明显增加(P<0.05,P<0.01),氟西汀组和中药高剂量组大鼠海马组织5-HT_(2A)R mRNA表达均明显降低(P<0.05,P<0.01)。结论:逍遥解郁方可显著提高PSD大鼠血浆5-HT及NE含量;其升高5-HT含量的机制可能与其上调大鼠海马组织5-HT_(1A)R mRNA表达、下调5-HT_(2A)R mRNA表达有关。

Objective: To study the mechanisms of Xiaoyao Jieyu Recipe in treating post-stroke depression ( PSD) in rats based onmonoaminergic neural signaling pathway. Methods: 50 SD rats were selected and randomly divided into the blank group,model group,fluoxetine group,Chinese medicine groups with low-and high-dose,10 rats in each group. First,the stroke model was induced by middlecerebral artery occlusion( MCAO) ,and then the depression model was established by chronic mild and unpredictable stress ( CMUS)combined with isolation feeding. After successful modeling,the rats in the drug treatment groups were treated with the corresponding drugsby intragastric administration for continuous 28 days. Forced swimming test and sugar water preference test were used to evaluate ratbehavior. The plasma concentrations of 5-hydroxytryptamine ( 5-HT) and norepinephrine ( NE) were detected by ELISA,and theexpressions of 5-HT1AR and 5-HT2AR mRNA in rat hippocampus were detected by RT-PCR. Results: Compared with the blank group,the immobility time of rats in the model group was obviously prolonged in the forced swimming test,and the struggle time was obviouslyshortened,and the sugar water preference was obviously decreased( P<0.01) . Compared with the model group,the immobility time of ratsin the fluoxetine group showed no obvious change( P>0.05) , the immobility time of rats in the Chinese medicine groups with low- andhigh-dose was obviously shortened( P<0.01) ; the struggle time of rats in all drug treatment groups was obviously prolonged( P<0.01) , andthe sugar water preference was significantly increased( P<0.05) . Compared with the blank group,the plasma contents of 5-HT and NE inrats of the model group were significantly decreased ( P<0.01) . Compared with the model group,the plasma contents of 5-HT and NE inrats of all drug treatment groups were significantly increased ( P<0.05) . Compared with the blank group,the expression of 5-HT1A RmRNA in hippocampal tissue of rats in the model group was significantly decreased,and the expression of 5-HT2A R mRNA wassignificantly increased ( P<0.01) . Compared with the model group,the expression of 5-HT1AR mRNA in hippocampal tissue of rats in alldrug treatment groups was significantly increased( P<0.05,P<0.01) ; and the expression of 5-HT2A R mRNA in rats of fluoxetine groupand Chinese medicine group with high-dose was significantly decreased ( P<0.05,P<0.01) . Conclusion: Xiaoyao Jieyu Recipe cansignificantly increase the plasma contents of 5-HT and NE in rats with post-stroke depression. The mechanism on the increase of 5-HT maybe related to the up-regulation of 5-HT1AR mRNA and down-regulation of 5-HT2AR mRNA in rat hippocampus.