目的 研究菖麻熄風片對幼齡注意力缺陷多動障礙（ADHD）模型鼠多動、沖動、注意力缺陷及前額葉、紋狀體、腦微透析液中神經(jīng)遞質水平和多巴胺受體的影響。方法 孕期尼古丁暴露（PNE）仔鼠隨機分為模型組、靜靈口服液（7.4 mL·kg⁻¹）組、鹽酸托莫西?。?7.5 mg·kg⁻¹）組和菖麻熄風片低、中、高劑量（生藥量2.4、4.8、9.6 g·kg⁻¹）組，另設同周齡C57BL/6J仔鼠為對照組，ig給藥14 d。自發(fā)性高血壓大鼠（SHR）隨機分為靜靈口服液（4 mL·kg⁻¹）組、鹽酸托莫西汀（10 mg·kg⁻¹）組和菖麻熄風片低、中、高劑量（生藥量1.4、2.8、5.6 g·kg⁻¹）組，另設同周齡WKY大鼠為對照組，ig給藥14 d。采用曠場實驗、Y迷宮實驗和高架十字迷宮實驗檢測PNE仔鼠和SHR的多動、沖動行為以及注意力、學習能力；ELISA法檢測SHR前額葉、紋狀體環(huán)磷酸腺苷（cAMP）含量；免疫組化檢測SHR大腦前額葉、紋狀體中多巴胺受體D1（DRD1）、多巴胺受體D2（DRD2）的表達；高效液相色譜-質譜聯(lián)用技術（HPLC-MS）檢測SHR前額葉、紋狀體、腦微透析液中去甲腎上腺素（NE）、多巴胺（DA）及其代謝終產(chǎn)物3-甲氧基-4-羥基乙酸（HVA）的水平變化。結果 與模型組比較，PNE仔鼠給藥14 d，曠場實驗中菖麻熄風片中、高劑量組運動總距離及平均速度顯著減少（P＜0.05、0.01），Y迷宮實驗中菖麻熄風片低、高劑量組正確反應次數(shù)顯著增加（P＜0.01）。與模型組比較，SHR給藥7 d，曠場實驗中菖麻熄風片各劑量組運動總距離及平均速度顯著減少（P＜0.05、0.01），高架十字迷宮實驗中菖麻熄風片中、高劑量組進入開臂次數(shù)顯著減少（P＜0.05、0.01），高劑量組開臂停留時間顯著縮短（P＜0.05）；給藥14 d，曠場實驗中菖麻熄風片中、高劑量組運動距離及運動速度顯著減少（P＜0.05、0.01），各劑量組運動軌跡逐漸向周圍分布，中心區(qū)運動軌跡減少；高劑量組前額葉中NE水平顯著升高（P＜0.01）、紋狀體中DRD2陽性面積顯著減少（P＜0.05）。結論 菖麻熄風片能夠通過增加前額葉NE水平、降低紋狀體中DRD2表達，改善幼齡動物多動、沖動及注意力缺陷情況，提高幼齡動物的記憶能力，具有治療幼齡ADHD的藥理活性。

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 groups (P < 0.05, 0.01). Compared with the model group, after 7 days of administration in SHR, the total distance traveled and average speed in the open field test were significantly reduced in all dose groups of CXT (P < 0.05, 0.01), and the number of entries into the open arms in the elevated plus maze test was significantly reduced in the medium and high-dose groups (P < 0.05, 0.01), with the high-dose group showing a significant decrease in the time spent in the open arms (P < 0.05); after 14 days of administration, the total distance traveled and average speed in the open field test were significantly reduced in the medium and high-dose groups (P < 0.05, 0.01), and the movement trajectories gradually distributed towards the periphery, with a reduction in the movement trajectories in the central area; the NE level in the prefrontal cortex of the high-dose group was significantly increased (P < 0.01), and the positive area of DRD2 in the striatum was significantly reduced (P < 0.05). Conclusion CXT can improve the hyperactivity, impulsivity and attention deficit in young animals, as well as enhance their memory ability, by increasing the level of NE in the prefrontal lobe and reducing the expression of DRD2 in the striatum. It possesses pharmacological activity for the treatment of pediatric ADHD.

R285.5