FTY720对卒中后抑郁大鼠单胺类神经递质影响的实验研究  

Effects of FTY720 on monoamine neurotransmitters in rats with post-stroke depression

作　　者：王奕丹 张磊 王建楠 伍慧茹 张玲 杨洋 隋汝波 WANG Yidan;ZHANG Lei;WANG Jiannan;WU Huiru;ZHANG Ling;YANG Yang;SUI Rubo(Department of Neurology,the First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000;China.2.Department of Nursing,Jinzhou Medical University,Jinzhou 121000)

机构地区：[1]锦州医科大学附属第一医院神经内科,辽宁锦州121000 [2]锦州医科大学护理学院,辽宁锦州121000

出　　处：《中国比较医学杂志》2021年第4期38-43,共6页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金项目(81371461,81241050);辽宁省教育厅科技项目(JYTJCZR201903);辽宁省科学技术计划项目(2019-ZD-0802)。

摘　　要：目的探究芬戈莫德(Fingolimod,FTY720)对卒中后抑郁(post-stroke depression,PSD)大鼠行为学及单胺类神经递质的干预作用。方法50只雄性SD大鼠随机分为假手术组、卒中组、PSD组、氟西汀(Fluoxetine,FLU)组及FLU联合FTY720治疗组。采取大脑中动脉线栓法建立局灶性脑缺血大鼠模型,联合慢性不可预见的温和性应激(chronic unpredictable mild stress,CUMS)及孤养法制备PSD大鼠模型。在应激第1、8、15、22、29天评估各组大鼠行为学指标,第29天处死大鼠,测定各组大鼠海马中单胺类神经递质的含量及单胺类神经递质合成限速酶的表达。结果与假手术组及卒中组比较,PSD组大鼠同一时间点旷野实验得分、蔗糖水消耗比例显著减少(P<0.05);海马中5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)含量显著降低(P<0.05);色氨酸羟化酶2(tryptophan hydroxylase2,TPH2)mRNA、酪氨酸羟化酶(tyrosine hydroxylase,TH)mRNA的表达下降(P<0.05)。与PSD组比较,氟西汀组及联合治疗组大鼠同一时间点旷野实验得分、蔗糖水消耗比例升高(P<0.05);海马中5-HT、NE、DA含量升高(P<0.05);TPH2 mRNA、TH mRNA的表达上调(P<0.05)。两组间进一步比较发现联合治疗组治疗效果更为显著,差异具有统计学意义(P<0.05)。结论FTY720对PSD大鼠的抑郁样行为具有改善作用,而这种作用与提高单胺类神经递质的水平有关。Objective To explore the effect of FTY720 on the behavior and monoamine neurotransmitters of poststroke depression rats.Methods Fifty male SD rats were randomly divided into sham operation,stroke,PSD,FLU,and FLU+FTY720 groups(n=10 each).The middle cerebral artery thread embolization method was used to establish a focal cerebral ischemia rat model.The PSD rat model was established by combining chronic unpredictable mild stress and isolation method.At 1,8,15,22,and 29 days of stimulation,the behavioral indexes of rats in each group were evaluated.The rats were sacrificed on day 29 and the content of monoamine neurotransmitters and expression of the rate-limiting enzyme of monoamine neurotransmitter synthesis in the hippocampus of rats in each group were analyzed.Results Compared with sham operation and stroke groups,the open field test score and volume ratio of sucrose water consumption of the PSD group were significantly reduced at the same time points(P<0.05).Levels of 5-HT,NE,and DA were significantly reduced in the hippocampus(P<0.05).Expression of TPH2 and TH mRNAs was decreased in the hippocampus(P<0.05).Compared with the PSD group,the open field test score and volume ratio of sucrose water consumption of FLU and FLU+FTY720 groups were increased at the same time points(P<0.05).Levels of 5-HT,NE,and DA were increased in the hippocampus(P<0.05).Expression of TPH2 and TH mRNAs was upregulated in hippocampus(P<0.05).Conclusions FTY720 improves the depression-like behavior of PSD rats and its effect is related to increasing the levels of monoamine neurotransmitters.

关 键 词：卒中后抑郁 芬戈莫德 单胺类神经递质 海马 

分 类 号：R-33[医药卫生]