黄芩素对注意缺陷多动障碍大鼠前额叶皮质AC-cAMP-PKA信号通路的调控作用

目的研究黄芩素对注意缺陷多动障碍(ADHD)模型SHR大鼠自发性活动、冲动、学习记忆等行为学影响及对前额叶皮质腺苷酸环化酶(AC)-环磷酸腺苷(c AMP)-蛋白激酶A(PKA)信号通路的调控作用。方法将50只4周龄SHR大鼠随机分为模型组、哌醋甲酯组(2 mg/kg)、黄芩素低、中、高剂量组(100、200、400 mg/kg)另设WKY幼鼠为正常对照组,每组10只,在大鼠夜周期连续灌胃4周。采用开场实验、高架十字迷宫、新物体识别实验评估大鼠自发性行为、冲动行为及学习记忆功能,酶联免疫吸附法(ELISA)测定前额叶皮质中AC、c AMP、PKA含量。结果黄芩素高、中剂量组可以减少SHR大鼠在开场实验中的总运动距离(P0.05),而黄芩素3个剂量组均能减少大鼠直立次数(P0.05)。黄芩素中剂量组可明显降低大鼠进入高架十字迷宫开臂次数(P0.05),而黄芩素3个剂量组均可不同程度地减少大鼠在开臂停留时间(P0.05);黄芩素中剂量组可明显增高SHR大鼠在新物体识别实验测试期对新物体的偏好指数(P0.05)。黄芩素3个剂量组均可明显增加SHR大鼠前额叶皮质中AC及c AMP含量(P0.05),而黄芩素中、高剂量组又可显著增加大鼠前额叶皮质中PKA含量(P0.05)。结论黄芩素可以减少ADHD模型大鼠的自发性活动及冲动行为,改善其学习记忆能力,其机制可能与上调前额叶皮质中AC、c AMP、PKA的表达有关。

Effects of baicalein on AC-cAMP-PKA signaling pathway in prefrontal cortex of rats with attentional deficit hyperactivity disorder

Objective To study the effects of baicalein on spontaneous activity, impulsivity, learning-memorial ability,and the adenylate cyclase(AC)-cyclic adenosine monophosphate(cAMP)-protein ki-nase A(PKA)signaling pathway in prefrontal cortex(PFC)of rats with attention deficit hyperactivity disorder(ADHD).Methods Fifty 4-week-old SHR rats were randomly divided into the model group,methylphenidate(MPH)group(2 mg/kg), and low-dose, mid-dose and high-dose(100, 200, 400 mg/kg)baicalein groups,and WKY rats of the same age were selected as the normal control group(n=10 in each group).Rats were orally gavaged for 4 weeks in the dark-phase.Open field test(OFT),ele-vated plus maze(EPM)and novel object recognition test(NORT)were conducted to evaluate the spon-taneous activity, impulsivity and learning-memorial ability of rats individually at the end of treatment. AC,cAMP and PKA quantity were determined with enzyme-linked immunosorbent(ELISA)method. Results Movement distance in OFT was reduced in high-dose baicalein group and mid-dose baicalein group(P<0.05)afterwards.Vertical movements also decreased in all baicalein groups.Percentage of the times entering the open arms in the EPM was significantly reduced in the mid-dose baicalein group(P<0.05);staying duration in the total period in the EPM was also reduced in all baicalein groups(P<0. 05).The preference index in the testing phase of NORT increased in the mid-dose baicalein group(P<0.05).Levels of AC and cAMP in the PFC increased in all baicalein groups(P<0.05), while tPKA increased in high-dose and mid-dose baicalein group(P<0.05).Conclusion Baicalein could increase the levels of AC,cAMP and PKA in PFC of ADHD rats, which may shed some light to the mechanism how baicalein could relieve the spontaneous activity and impulsivity,improve learning-memorial ability of ADHD rats.