注意缺陷多动障碍模型大鼠HPA轴功能的变化研究
|
摘要
目的:观察注意缺陷多动障碍(ADHD)模型动物自发性高血压大鼠(SHR)血清皮质酮(CORT)、促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放激素(CRH)水平及下丘脑糖皮质激素受体(GR)、糖皮质激素受体(MR)、CRH及海马GR、MR mRNA的表达情况,探讨SHR大鼠下丘脑-垂体-肾上腺轴(HPA)功能及相关影响因素。方法:以幼年SHR大鼠为ADHD模型组、Wistar京都大鼠(WKY)为对照组,采用ELISA法检测血清CORT、ACTH、CRH水平,RT-PCR法检测大鼠下丘脑GR、MR、CRH及海马GR、MR mRNA的表达水平。结果:SHR大鼠血清CORT、ACTH水平明显低于WKY大鼠(P<0.01),血清CRH水平明显高于WKY大鼠(P<0.01),下丘脑及海马GR、MR mRNA的表达水平明显高于WKY大鼠(P<0.01),而下丘脑CRH mRNA表达则低于WKY大鼠(P<0.01)。结论:SHR大鼠HPA轴呈低反应性,可能与CRH启动障碍及下丘脑和海马GR、MR mRNA高表达相关。
Objective: To observe the Levels of serum CORT, ACTH and CRH in SHR rats, the expression of GR, MR and CRH mRNA in hypothalamus and GR, MR mRNA in hippocampus of the ADHD model animal SHR rat, and to explore the HPA axis function and related factors in SHR rats. Methods: Junior SHR rats were used as ADHD model group and WKY rats as control group. The levels of CORT, ACTH and CRH in serum were detected by ELISA, and the mRNA expressions of GR, MR, CRH in hypothalamus and GR, MR in hippocampus were detected by RT-PCR. Results: The levels of serum CORT and ACTH in SHR rats were significantly lower than those in WKY rats(P<0.01), and the levels of serum CRH were significantly higher than those in WKY rats(P<0.01). GR and MR mRNA expression levels in hypothalamus and hippocampus were significantly higher than those in WKY rats(P<0.01), while CRH mRNA expression in hypothalamus was significantly lower than that in WKY rats(P<0.01). Conclusion: The HPA axis of SHR rats showed hyporesponsiveness, which may be related to CRH priming disorder and high expression of GR and MR mRNA in hypothalamus and hippocampus.
Objective: To observe the Levels of serum CORT, ACTH and CRH in SHR rats, the expression of GR, MR and CRH mRNA in hypothalamus and GR, MR mRNA in hippocampus of the ADHD model animal SHR rat, and to explore the HPA axis function and related factors in SHR rats. Methods: Junior SHR rats were used as ADHD model group and WKY rats as control group. The levels of CORT, ACTH and CRH in serum were detected by ELISA, and the mRNA expressions of GR, MR, CRH in hypothalamus and GR, MR in hippocampus were detected by RT-PCR. Results: The levels of serum CORT and ACTH in SHR rats were significantly lower than those in WKY rats(P<0.01), and the levels of serum CRH were significantly higher than those in WKY rats(P<0.01). GR and MR mRNA expression levels in hypothalamus and hippocampus were significantly higher than those in WKY rats(P<0.01), while CRH mRNA expression in hypothalamus was significantly lower than that in WKY rats(P<0.01). Conclusion: The HPA axis of SHR rats showed hyporesponsiveness, which may be related to CRH priming disorder and high expression of GR and MR mRNA in hypothalamus and hippocampus.
引文
1 李世明,冯为,方芳,等.中国儿童注意缺陷多动障碍患病率Meta分析[J].中华流行病学杂志,2018,39(7) :993-998.
2 Rezaei G,Hosseini SA,Akbari Sari A,et al.Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents:A systematic review and meta-analysis[J].Med J Islam Repub Iran,2016,30:325.
3 郑杰,陈燕惠.注意缺陷多动障碍发病机制研究进展[J].中国当代儿科杂志,2018,20(9):775-778.
4 Kariyawasam SH,Zaw F,Handley SL.Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder[J].Neuro Endocrinol Lett,2002,23(1):45-48.
5 Shin DW,Lee SH.Blunted hypothalamo-pituitary-adrenal axis reactivity is associated with the poor intelligence performance in children with attention-deficit/hyperactivity disorder[J].Neuropediatrics,2007,8(6):298-303.
6 Freitag CM,H?nig S,Palmason H,et al.Cortisol awakening response in healthy children and children with ADHD:impact of comorbid disorders and psychosocial risk factors[J].Psychoneuroendocrinology,2009,34(7):1019-1028.
7 Isaksson J,Nilsson KW,Nyberg F,et al.Cortisol levels in children with attention-deficit/hyperactivity disorder[J].J Psychiatr Res,2012,46(11):1398-1405.
8 陈燕惠,陈辉,刘艳艳,等.注意力缺陷多动障碍儿童下丘脑-垂体-肾上腺轴的功能研究[J].中国当代儿科杂志,2009,11 (12):992-995.
9 柳昌炳.注意缺陷多动障碍倾向幼儿下丘脑-垂体-肾上腺皮质轴功能状态研究[J].浙江医学,2016,38 (13):1098-1110.
10 郑小兰,陈燕惠.注意缺陷多动障碍的实验动物模型[J].中华行为医学与脑科学杂志,2015,24(3):276-279.
11 Andersen SL.Changes in the second messenger cyclic AMP during development may underlie motoric symptoms in attention deficit/hyperactivity disorder (ADHD)[J].Behav Brain Res,2002,130(1-2):197-201.
12 Banegas I,Prieto I,Segarra AB,et al.Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine[J].Prog Neuropsychopharmacol Biol Psychiatry,2017,75:213-218.
13 Senft RA,Meddle SL,Baugh AT.Distribution and abundance of glucocorticoid and mineralocorticoid receptors throughout the brain of the great tit (parus major)[J].PLoS One,2016,11(2):e0148516.
14 David P,Joan L,Ryan B,et al.HPA axis genetic variation,pubertal status,and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children[J].Neuro Image,2015,109:1-11.
15 谢琳琪.SHR幼鼠不同脑区皮质酮及糖皮质激素受体水平对注意维持的影响[D].福州:福建医科大学,2015.
16 Wu LH,Cheng W,Yu M,et al.Nr3C1-Bhlhb2 axis dysregulation is involved in the development of attention deficit hyperactivity[J].Mol Neurobiol,2017,54(2):1196-1212.
2 Rezaei G,Hosseini SA,Akbari Sari A,et al.Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents:A systematic review and meta-analysis[J].Med J Islam Repub Iran,2016,30:325.
3 郑杰,陈燕惠.注意缺陷多动障碍发病机制研究进展[J].中国当代儿科杂志,2018,20(9):775-778.
4 Kariyawasam SH,Zaw F,Handley SL.Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder[J].Neuro Endocrinol Lett,2002,23(1):45-48.
5 Shin DW,Lee SH.Blunted hypothalamo-pituitary-adrenal axis reactivity is associated with the poor intelligence performance in children with attention-deficit/hyperactivity disorder[J].Neuropediatrics,2007,8(6):298-303.
6 Freitag CM,H?nig S,Palmason H,et al.Cortisol awakening response in healthy children and children with ADHD:impact of comorbid disorders and psychosocial risk factors[J].Psychoneuroendocrinology,2009,34(7):1019-1028.
7 Isaksson J,Nilsson KW,Nyberg F,et al.Cortisol levels in children with attention-deficit/hyperactivity disorder[J].J Psychiatr Res,2012,46(11):1398-1405.
8 陈燕惠,陈辉,刘艳艳,等.注意力缺陷多动障碍儿童下丘脑-垂体-肾上腺轴的功能研究[J].中国当代儿科杂志,2009,11 (12):992-995.
9 柳昌炳.注意缺陷多动障碍倾向幼儿下丘脑-垂体-肾上腺皮质轴功能状态研究[J].浙江医学,2016,38 (13):1098-1110.
10 郑小兰,陈燕惠.注意缺陷多动障碍的实验动物模型[J].中华行为医学与脑科学杂志,2015,24(3):276-279.
11 Andersen SL.Changes in the second messenger cyclic AMP during development may underlie motoric symptoms in attention deficit/hyperactivity disorder (ADHD)[J].Behav Brain Res,2002,130(1-2):197-201.
12 Banegas I,Prieto I,Segarra AB,et al.Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine[J].Prog Neuropsychopharmacol Biol Psychiatry,2017,75:213-218.
13 Senft RA,Meddle SL,Baugh AT.Distribution and abundance of glucocorticoid and mineralocorticoid receptors throughout the brain of the great tit (parus major)[J].PLoS One,2016,11(2):e0148516.
14 David P,Joan L,Ryan B,et al.HPA axis genetic variation,pubertal status,and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children[J].Neuro Image,2015,109:1-11.
15 谢琳琪.SHR幼鼠不同脑区皮质酮及糖皮质激素受体水平对注意维持的影响[D].福州:福建医科大学,2015.
16 Wu LH,Cheng W,Yu M,et al.Nr3C1-Bhlhb2 axis dysregulation is involved in the development of attention deficit hyperactivity[J].Mol Neurobiol,2017,54(2):1196-1212.