机构地区:[1]南京中医药大学,南京210029
出 处:《中国实验方剂学杂志》2011年第23期101-104,共4页Chinese Journal of Experimental Traditional Medical Formulae
基 金:教育部高等学校博士学科点专项科研基金(200803150003)
摘 要:目的:研究安神定志灵对注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)动物模型-自发性高血压大鼠(spontaneously hypertensive rat,SHR)纹状体多巴胺转运体(DAT)表达的影响,探讨该药治疗ADHD的作用机制。方法:30只SHR鼠随机分为5组(模型组、利他林组、安神定志灵高、中、低剂量组),每组6只,Wistar-Kyoto(WKY)大鼠6只作为正常对照组。安神定志灵高、中、低剂量组分别按生药剂量34.1,17.1,8.5 g.kg-1 ig;利他林组以2.1 mg.kg-1利他林ig;模型组和正常对照组以10 mL.kg-1生理盐水ig。连续给药2周后处死大鼠,取脑分别用RT-PCR和激光共聚焦显微镜检测各组大鼠纹状体多巴胺转运体(DAT)mRNA和蛋白表达水平。结果:大鼠纹状体中DAT的蛋白表达水平,组间存在差异(P<0.05),SHR模型组大鼠纹状体中DAT的蛋白表达与正常对照组比较显著增高(P<0.01);安神定志灵中、高剂量组DAT的蛋白表达显著低于模型组(P<0.01),利他林组DAT的蛋白表达显著低于模型组(P<0.05),安神定志灵低剂量组和模型组DAT蛋白表达相比无统计学意义。蛋白表达量从高到低依次为安神定志灵低剂量组、利他林组、安神定志灵中、高剂量组。结论:安神定志灵可以降低SHR大鼠纹状体中DAT mRNA及蛋白的表达水平,减少突触前神经元对DA的重摄取,增加突触间隙的DA浓度,改善了中枢DA的神经信号传导功能,起到对ADHD的治疗作用。Objective:To study the effects of Anshen Dingzhi Ling(ADL) on expression of dopamine transporter(DAT) of spontaneously hypertensive(SHR) rats' striatum and the mechanism of this medicine to treat with ADHD.Method: Thirty SHR rats were randomly divided into 5 groups including model group,ritalin group,ADL high dose group,ADL medium dose group and ADL low dose group,6 rats each group,meantime,6 Wistar-Kyoto rats constitute normal control group.The dosages of the 3 groups of ADL were 34.1,17.1,8.5 g·kg-1,ig respectively and the dosage of ritalin group is 2.1 mg·kg-1,ig,as for the model group or normal control,rats were given physiological saline as per 10 mL·kg-1,ig.After 2-week,the rats in experiments were killed and separate the brain tissues,then examine the expression of striatum DAT protein or mRNA of each group with RT-PCR as well as laser scanning confocal microscope.Result: Statistic difference of DAT protein expression was observed among different groups(P0.05).Comparing with the normal control group,the DAT protein expression of striatum of SHR model group was higher obviously(P0.01);the DRT protein expression of ADL medium or high group was lower than model group(P0.01),meanwhile,the protein expression of ritalin group was lower than model group also(P0.05),but no statistic difference was observed between groups of low-dose ADL group and model in expression of DAT protein expression.The protein expression levels from the lower to the higher were ADL low dose group,ritalin group,ADL medium group as well as ADL high dose group.Conclusion: ADL has the potent to depress the expression of DAT mRNA as well as protein in SHR rat striatum,to block the reuptaking DA process performed by presynaptic neuron,and then to increase the DA concentration in synaptic clefts,to improve the conduction function of nerve signals of centrum DA,to play a role to treat with ADHD after all.
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