菖麻熄风片改善幼龄鼠注意力缺陷多动障碍及作用机制研究  

Effect of Changma Xifeng Tablet on symptoms and mechanism of attention deficit hyperactivity disorder in young animals

作　　者：荆宝琴 张杉杉 李冬芝 韩冰 乔鑫[1] 姚洪艳 JING Baoqin;ZHANG Shanshan;LI Dongzhi;HAN Bing;QIAO Xin;YAO Hongyan(School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Tianjin Tiancheng Drug Assessment Research Co.,Ltd.,Tianjin 300301,China;Heilongjiang Jiren Pharmaceutical Co.,Ltd.,Harbin 150025,China;Tianjin Engineering Research Center of Drug Preclinical Assessment Technology,Tianjin 300301,China;State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine,Tianjin 300301,China)

机构地区：[1]天津医科大学药学院,天津300070 [2]天津天诚新药评价有限公司,天津300301 [3]黑龙江省济仁药业有限公司,黑龙江哈尔滨150025 [4]天津市新药非临床评价技术工程中心,天津300301 [5]药物成药性评价与系统转化全国重点实验室,天津300301

出　　处：《药物评价研究》2025年第3期679-688,共10页Drug Evaluation Research

摘　　要：目的研究菖麻熄风片对幼龄注意力缺陷多动障碍(ADHD)模型鼠多动、冲动、注意力缺陷及前额叶、纹状体、脑微透析液中神经递质水平和多巴胺受体的影响。方法孕期尼古丁暴露(PNE)仔鼠随机分为模型组、静灵口服液(7.4 mL·kg^(−1))组、盐酸托莫西汀(17.5 mg·kg^(−1))组和菖麻熄风片低、中、高剂量(生药量2.4、4.8、9.6 g·kg^(−1))组,另设同周龄C57BL/6J仔鼠为对照组,ig给药14 d。自发性高血压大鼠(SHR)随机分为静灵口服液(4 mL·kg^(−1))组、盐酸托莫西汀(10 mg·kg^(−1))组和菖麻熄风片低、中、高剂量(生药量1.4、2.8、5.6 g·kg^(−1))组,另设同周龄WKY大鼠为对照组,ig给药14 d。采用旷场实验、Y迷宫实验和高架十字迷宫实验检测PNE仔鼠和SHR的多动、冲动行为以及注意力、学习能力;ELISA法检测SHR前额叶、纹状体环磷酸腺苷(cAMP)含量;免疫组化检测SHR大脑前额叶、纹状体中多巴胺受体D1(DRD1)、多巴胺受体D2(DRD2)的表达;高效液相色谱-质谱联用技术(HPLC-MS)检测SHR前额叶、纹状体、脑微透析液中去甲肾上腺素(NE)、多巴胺(DA)及其代谢终产物3-甲氧基-4-羟基乙酸(HVA)的水平变化。结果与模型组比较,PNE仔鼠给药14 d,旷场实验中菖麻熄风片中、高剂量组运动总距离及平均速度显著减少(P<0.05、0.01),Y迷宫实验中菖麻熄风片低、高剂量组正确反应次数显著增加(P<0.01)。与模型组比较,SHR给药7 d,旷场实验中菖麻熄风片各剂量组运动总距离及平均速度显著减少(P<0.05、0.01),高架十字迷宫实验中菖麻熄风片中、高剂量组进入开臂次数显著减少(P<0.05、0.01),高剂量组开臂停留时间显著缩短(P<0.05);给药14 d,旷场实验中菖麻熄风片中、高剂量组运动距离及运动速度显著减少(P<0.05、0.01),各剂量组运动轨迹逐渐向周围分布,中心区运动轨迹减少;高剂量组前额叶中NE水平显著升高(P<0.01)、纹状体中DRD2阳Objective To study the effects of Changma Xifeng Tablet(CXT)on hyperactivity,impulsivity and attention deficit of young attention deficit hyperactivity disorder(ADHD)model rats and the levels of neurotransmitters and dopamine receptors in the prefrontal lobe,striatum and brain microdialysis solution.Methods Prenatal nicotine exposure(PNE)mice were randomly divided into model group,CXT low-dose,medium-dose,and high-dose groups(crude drug dose of 2.4、4.8、9.6 g·kg^(−1)),Jingling oral liquid group(7.4 mL·kg^(−1)),and tomoxetine hydrochloride group(17.5 mg·kg^(−1)),C57BL/6J mice of the same week were also assigned as normal group.All group were administered by gavage for 14 days.Spontaneously hypertensive rats(SHR)were randomly divided into model group,CXT low-dose,medium-dose,and high-dose groups(crude drug dose of 1.4、2.8、5.6 g·kg^(−1)),Jingling oral liquid group(4 mL·kg^(−1)),and tomoxetine hydrochloride group(10 mg·kg^(−1)),and wistar kyoto rats(WKY)of the same week as normal group.Open field experiment,Y maze experiment and elevated cross maze experiment were used to detect hyperactivity,impulsive behavior,attention and learning ability of PNE mice and SHR rats.The cyclic adenosine monophosphate(cAMP)content in the prefrontal lobe and striatum of SHR rats was detected by ELISA.The expression of DRD1 and DRD2 of dopamine receptors in the prefrontal lobe and striatum of SHR rats was detected by immunohistochemistry.High Performance liquid chromatography-mass spectrometry(HPLC-MS)was used to determine norepinephrine(NE),dopamine(DA)and the metabolite 3-methoxy-4-hydroxy acetic acid(HVA)in the prefrontal lobe,striatum and brain microdialysis solution of SHR.Results Compared with the model group,after 14 days of administration in PNE pups,the total distance traveled and average speed in the open field test were significantly reduced in the medium and high-dose groups of CXT(P<0.05,0.01),and the number of correct responses in the Y-maze test was significantly increased in the low and high-dose

关 键 词：菖麻熄风片 注意力缺陷多动障碍 多巴胺受体 自发性高血压大鼠 孕期尼古丁暴露 去甲肾上腺素 

分 类 号：R285.5[医药卫生—中药学]