黄芩苷对注意缺陷多动障碍模型大鼠行为学特征的影响研究

Effect of baicalin on behavioral characteristics of rats with attention deficit hyperactivity disorder

目的研究黄芩苷对注意缺陷多动障碍(ADHD)模型大鼠行为学特征的影响,为黄芩苷治疗ADHD的进一步研究提供依据。方法将40只SHR大鼠随机分为模型组、盐酸哌甲酯组及黄芩苷低、中、高剂量组,每组8只,另设8只WKY大鼠为正常对照组。盐酸哌甲酯组(0.07 mg/mL)及黄芩苷低剂量(3.33 mg/mL)、中剂量(6.67 mg/mL)、高剂量(10 mg/mL)组分别按体重(1.5 mL/100 g)给予对应药物灌胃,正常对照组、模型组给予等量生理盐水灌胃,各组大鼠灌胃4周,每日2次。旷场实验观察实验第0天及灌胃后7、14、21、28 d各组大鼠的总运动距离及平均运动速度,评估药物对大鼠多动、冲动行为的控制作用;Morris水迷宫实验观察各组大鼠的潜伏期、目标象限活动比率及穿越平台次数,评估药物对大鼠注意力的影响。结果旷场实验数据显示,第0天,模型组及各用药组大鼠的总运动距离及平均运动速度均显著高于正常对照组(P<0.05);第7天,盐酸哌甲酯组总运动距离及平均运动速度较模型组显著降低(P<0.05);第14天,盐酸哌甲酯组及黄芩苷高剂量组大鼠在总运动距离及平均运动速度上均较模型组显著降低(P<0.05);第21天及第28天,黄芩苷各剂量组在总运动距离及平均运动速度上较模型组均呈不断下降趋势(P<0.05)。水迷宫空间探索实验结果显示,盐酸哌甲酯组及黄芩苷中、高剂量组目标象限停留时间比率显著高于模型组(P<0.05),盐酸哌甲酯组、黄芩苷高剂量组目标象限运动距离所占比率亦显著高于模型组(P<0.05);黄芩苷高剂量组穿越平台次数高于其余各组(P<0.05)。结论黄芩苷及盐酸哌甲酯均能够调控ADHD模型SHR大鼠的运动能力及学习记忆能力,从而控制ADHD多动、冲动及注意力不集中的核心症状;黄芩苷药效呈剂量依赖性,高剂量黄芩苷疗效最为显著,但其药效的发挥迟于盐酸哌甲酯。

Objective To investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder（ADHD）,and to provide a basis for further research on baicalin in the treatment of ADHD.Methods A total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride（MPH） group,and low-,medium-,and high-dose baicalin groups,with 8 rats in each group.Eight WKY rats were selected as normal control group.The rats in the MPH group（0.07 mg/mL） and the low-（3.33 mg/mL）,medium-（6.67 mg/mL）,and high-dose（10 mg/mL） baicalin groups were given the corresponding drugs（1.5 mL/100 g） by gavage twice a day,and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day.The course of treatment was 4 weeks for all groups.The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7,14,21,and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior.The Morris water maze test was used to observe the latency,time spent in the target quadrant,and number of platform crossings and to evaluate the effects of drugs on attention.Results The open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0（P〈0.05）.On day 7,the MPH group had significant reductions in total moving distance and average moving speed compared with the model group（P〈0.05）.On day 14,the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group（P〈0.05）.The data on days 21 and 28 showed that compared with the model group,the low-,medium-,and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed（P〈0.05）.The water maze test showed that compared with the model group,the MPH group and the medium-and high-dose baicalin groups had a significantly longer time spent in the target quadrant（P〈0.05）,and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance（P〈0.05）.The high-dose baicalin group had the highest number of platform crossings among all groups（P〈0.05）.Conclusions Both baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD,i.e.,hyperactivity,impulsive behavior,and inattention.Baicalin exerts its effect in a dose-dependent manner,and high-dose baicalin has the most significant effect,but compared with MPH,it needs a longer time to play its therapeutic effect.