首页|柴贝止痫汤对癫痫—抑郁共病模型大鼠大脑皮层及海马中5-HTT、5-HT1AR、5-HT2AR和DA2R表达的影响

柴贝止痫汤对癫痫—抑郁共病模型大鼠大脑皮层及海马中5-HTT、5-HT1AR、5-HT2AR和DA2R表达的影响

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目的 观察柴贝止痫汤对氯化锂—匹罗卡品慢性颞叶癫痫—抑郁共病模型大鼠大脑皮层及海马中5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT)、5-羟色胺受体(5-hydroxytryptamine repreceptor,5-HTR)(5-HT1AR、5-HT2AR)和多巴胺(dopamine,DA)受体(DA2R)表达的影响,探讨柴贝止痫汤对癫痫—抑郁共病的干预机制.方法 建立氯化锂—匹罗卡品慢性颞叶癫痫—抑郁共病大鼠模型.造模成功后,将大鼠随机分为6组:正常组、模型组、西药组(西酞普兰给药)和柴贝止痫汤低、中、高剂量组,连续灌胃给药14天,每天2次.干预后,通过糖水偏好及强迫游泳实验进行抑郁行为学监测;酶联免疫吸附法检测大鼠大脑皮层及海马中5-HT、DA含量;实时定量PCR法检测大鼠大脑皮层及海马中5-HTT、5-HT1AR、5-HT2AR和DA2 R基因的mRNA表达水平;蛋白免疫印迹法检测大鼠大脑皮层及海马中5-HTT、5-HT1AR、5-HT2AR和DA2R的蛋白表达水平.结果 药物干预后,与模型组相比,柴贝止痫汤中、高剂量组大鼠糖水消耗量显著增加(P<0.01),不动时间显著减少(P<0.01);与模型组比较,柴贝止痫汤中(P<0.05)、高剂量组(P<0.01)大鼠大脑皮层及海马中5-HT含量、皮层中DA含量升高,高剂量组(P<0.05)大鼠大脑海马中DA含量升高;与模型组相比,柴贝止痫汤高剂量组大鼠大脑皮层5-HTT mRNA表达降低(P<0.01),而海马中5-HTT mRNA表达升高(P<0.05);同时,柴贝止痫汤高剂量组大鼠大脑皮层和海马中5-HT1AR mRNA表达明显升高(P<0.05),蛋白表达水平与mRNA水平表达一致.5-HT2AR和DA2R的mRNA和蛋白表达水平在处理前后均无变化.结论 柴贝止痫汤能够通过下调慢性颞叶癫痫—抑郁共病模型大鼠大脑皮层5-HTT,上调海马5-HTT,以及上调大脑皮层和海马中5-HT1AR的表达水平,改善抑郁行为.
Effect of Chaibei Zhixian Decoction on the expression of 5-HTT,5-HT1AR,5-HT2AR and DA2R in cerebral cortex and hippocampus of epilepsy-associated depression diseased rats
Objective This study aimed to investigate whether Chaibei Zhixian Decoction alleviate epilepsy-associated depression disease through the regulation of 5-HTT,5-HT1AR,5-HT2AR and DA2R in the cerebral cortex and hippocampus of lithium chloride(LiCl)-pilocarpine-induced epilepsy-associated depression rat model.Methods The lithium pilocarpine chronic temporal lobe epilepsy depression co-disease rat model was established.The rats were randomly divided into 6 groups:the control group,the model group,the positive drug group and the low,middle and high dose of Chaibei Zhixian Decoction groups.The rats were administered orally for 14 consecutive days,twice a day.After intervention,the behavioral monitoring of depression was carried out by sucrose preference test and forced swimming test.The levels of 5-HT and DA in rat cerebral cortex and hippocampus were detected by ELISA.The mRNA expression levels of5-HTT,5-HT1AR,5-HT2AR and DA2R genes in rat cerebral cortex and hippocampus were detected by real-time quantitative PCR.The method of western blotting was used to detect the protein expression levels of 5-HTT,5-HT1AR,5-HT2AR and DA2R in the cerebral cortex and hippocampus of rats.Results After Chaibei Zhixian Decoction intervention,compared with the model group,the sucrose consumption of the rats treated with middle and high doses of Chaibei Zhixian Decoction was significantly increased(P<0.01)and the immobility time was decreased(P<0.01).Compared with the model group,the levels of 5-HT and DA in the cortex in the middle(P<0.05)and high(P<0.01)doses of Chaibei Zhixian Decoction were increased.DA in the hippocampus of high doses were increased(P<0.01).Compared with the model group,5-HTT mRNA expression in the cerebral cortex was significantly decreased(P<0.01),while 5-HTT mRNA expression in the hippocampus was significantly increased(P<0.05).Furthermore,5-HT1A R mRNA expression in both cerebral cortex and hippocampus was significantly increased(P<0.05),and the protein expression level was consistent with the mRNA level.On the other hand,the mRNA and protein levels of-5HT2AR and DA2R did not change before and after drug treatment.Conclusion Chaibei Zhixian Decoction has the functions of down-regulation of 5-HTT in cerebral cortex,up-regulation of 5-HTT in hippocampus,and up-regulation of 5-HT1AR expression in cerebral cortex and hippocampus of rats with chronic temporal lobe epilepsy depression comorbidity,and improving depressive behavior.

Chaibei Zhixian Decoctionepilepsy-associated depression5-HTT5-HTRDA2R

王越、刘金民、王凯悦、徐薇薇

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300150 天津中医药大学第二附属医院急诊科

北京中医药大学东方医院脑病一科

柴贝止痫汤 癫痫—抑郁共病 5-羟色胺转运体 5-羟色胺受体 多巴胺受体

天津市教委科研计划项目

2019KJ049

2024

环球中医药
中华国际医学交流基金会

环球中医药

CSTPCD
影响因子:1.553
ISSN:1674-1749
年,卷(期):2024.17(2)
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