安神定志灵对注意缺陷多动障碍模型大鼠的作用研究  

Study on the Effect of Anshen Dingzhi Ling on AttentionDeficit Hyperactivity Disorder Model Rats

作　　者：孙继超 张碧霞 朱万青 王丹谊[1] 李伟伟[1] 庞丽红[2] 李亚群[3] 谢胜[1] SUN Jichao;ZHANG Bixia;ZHU Wanqing;WANG Danyi;LI Weiwei;PANG Lihong;LI Yaqun;XIE Sheng(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Taizhou Hospital of Traditional Chinese Medicine,Taizhou 225300,China)

机构地区：[1]广西中医药大学第一附属医院,南宁530023 [2]广西医科大学第一附属医院,南宁530021 [3]泰州市中医医院,江苏泰州225300

出　　处：《中国中医基础医学杂志》2024年第10期1702-1709,共8页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81804146,82260953);广西自然科学基金项目(2017JJB140344y,2020GXNSFAA297166);广西高校中青年教师基础能力提升项目(2018KY0281);广西中医药大学引进博士科研启动基金项目(2017BS046)。

摘　　要：目的观察安神定志灵对注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)模型大鼠的影响并探讨其作用机制。方法选择Wistar京都大鼠(Wistar Kyoto,WKY)纳入正常组。自发性高血压大鼠(spontaneously hypertensive rat,SHR)作为ADHD模型动物,随机分为模型组,托莫西汀组,安神定志灵低、中、高剂量组,每组10只。予相应药物灌胃4周后,ELISA法测定大鼠前额叶、纹状体组织中白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α、转化生长因子(transforming growth factor,TGF)-β1、干扰素(interferon,IFN)-α1、IFN-β1的含量。Western blot和RT-qPCR检测大鼠前额叶、纹状体组织中神经生长因子(nerve growth factor,NGF)、胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)、脑源性神经营养因子(brain derived neurotrophic factor,BDNF)、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9表达。结果与正常组比较,模型组大鼠前额叶与纹状体IL-1β、IL-6、TNF-α及TGF-β1表达增加(P<0.05),IFN-α1和IFN-β1表达降低(P<0.01);MMP-2、MMP-9的蛋白和mRNA水平升高(P<0.01);NGF、GDNF、BDNF蛋白和mRNA水平降低(P<0.05)。安神定志灵高剂量对模型大鼠上述指标均有明显调节作用(P<0.05)。结论安神定志灵能够通过抑制ADHD模型大鼠前额叶与纹状体炎症反应发挥神经元保护作用。Objective To observe the effects of Anshen Dingzhi Ling on attention deficit hyperactivity disorder(ADHD)model rats,and explore its mechanism.Methods Wistar Kyoto rats(WKY)were selected as the normal group,and the spontaneously hypertensive rats(SHR)were selected as the models.SHR were randomly divided into model group,atomoxetine group,Anshen Dingzhi Ling low-dose,medium-dose and high-dose group,10 rats in each group.Each group of rats was given corresponding drugs by gavage.After 4 weeks of intervention,prefrontal cortex and striatum of rats were collected.The levels of IL-1β,IL-6,TNF-α,TGF-β1,IFN-α1 and IFN-β1 in both prefrontal cortex and striatum were determined by ELISA.Western blot and Real-time qPCR were used to detect the expressions of NGF,GDNF,BDNF,MMP-2 and MMP-9.Results Compared with the normal group,the expression of IL-1β,IL-6,TNF-αand TGF-β1,as well as the protein and gene expression of MMP-2 and MMP-9 increased(P<0.05),while the expression of IFN-α1 and IFN-β1,and the protein and gene expressions of NGF,GDNF and BDNF decreased(P<0.05)in the prefrontal cortex and striatum of rats in the model group.High dose of Anshen Dingzhi Ling could significantly regulate the above indexes in the model rats(P<0.05).Conclusion Anshen Dingzhi Ling can protect neurons by inhibiting the inflammation in the prefrontal cortex and striatum of ADHD model rats.

关 键 词：注意缺陷多动障碍 安神定志灵 自发性高血压大鼠 炎症因子 

分 类 号：R285.5[医药卫生—中药学]