摘要
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-HT_(1A)R、5-HT_(2A)R)和多巴胺(dopamine, DA)受体(DA_(2)R)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-HT_(1A)R、5-HT_(2A)R和DA_(2)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-HT_(1A)R、5-HT_(2A)R和DA_(2)R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-HT_(1A)R 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-HT_(2A)R和DA_(2)R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-HT_(1A)R的表达水平,改善抑郁行为。
Objective This study aimed to investigate whether Chaibei Zhixian Decoction alleviate epilepsy-associated depression disease through the regulation of 5-HTT,5-HT_(1A)R,5-HT_(2A)R and DA_(2)R 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 of 5-HTT,5-HT_(1A)R,5-HT_(2A)R and DA_(2)R 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-HT_(1A)R,5-HT_(2A)R and DA_(2)R 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-HT_(1A)R mRNA expression in both cerebral cortex and hippocampus was significantly increased(P<0.05),and the protein expression level was consiste
作者
王越
刘金民
王凯悦
徐薇薇
WANG Yue;LIU Jinmin;WANG Kaiyue;XU Weiwei(The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300150,China;不详)
出处
《环球中医药》
CAS
2024年第2期196-202,共7页
Global Traditional Chinese Medicine
基金
天津市教委科研计划项目(2019KJ049)。
