甘麦大枣汤对ADHD动物模型SHR大鼠DRD1、DRD2与肠道菌群分布的影响  

Effects of Ganmai Dazao Decoction on DRD1, DRD2 and Intestinal Microflora Distribution in SHR Rats of ADHD Animal Model

作　　者：安家盛 周正[2] 党伟利[2] 景佳星 高绍芳 An Jiasheng;Zhou Zheng;Dang Weili;Jing Jiaxing;Gao Shaofang(College of Integrated Traditional Chinese and Western Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050091,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,China)

机构地区：[1]河北中医学院中西医结合学院,石家庄050091 [2]河南中医药大学第一附属医院,郑州450003

出　　处：《世界科学技术-中医药现代化》2022年第2期546-553,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河南省中医药管理局河南省中医药科学研究专题项目(2017ZY2095):柴芍制动方对儿童多动症患儿多动、冲动行为的临床研究,负责人:周正。

摘　　要：目的研究甘麦大枣汤对注意缺陷多动障碍(Attention deficit-hyperactivity disorder,ADHD)模型动物自发性高血压大鼠(Spontaneous hypertension rat,SHR)行为学变化、前额叶皮质层多巴胺受体D1(Dopamine Receptor D1,DRD1)、多巴胺受体D2(Dopamine Receptor D2,DRD2)的表达以及肠道菌群分布的影响。方法SHR大鼠随机分为甘麦大枣汤组(GMDZ组),利他林组(MPH组)和模型组(Model组),每组8只,另设8只韦斯达-京都大鼠(wistar-kyoto rat,WKY)大鼠为空白对照组(Control组),适应性饲养7天后,各组大鼠药物灌胃21天。进行为期6天的Morris水迷宫实验评估药物对SHR大鼠学习能力、冲动、多动行为的影响;通过蛋白免疫印迹(Western Blot,WB)法与反转录实时荧光定量PCR(Real Time Quantitative PCR,RT-qPCR)检测前额叶皮质层DRD1和DRD2蛋白与信使RNA(messenger RNA,mRNA)表达变化;通过16S高通量测序检测药物对肠道菌群分布的影响。结果与模型组相比,甘麦大枣汤组和利他林组平均潜伏期缩短,目标象限停留时间延长,穿越平台次数增多,平均速度减慢,总路程缩短。与模型组相比,甘麦大枣汤组和利他林组大鼠DRD1和DRD2的蛋白和mRNA表达水平显著升高。16S高通量测序结果显示,空白对照组与其他三组之间粪便物种多样性存在较大差异;模型组与甘麦大枣汤组、模型组与利他林组之间粪便物种多样性存在一定差异;甘麦大枣汤组与利他林组之间粪便物种多样性差异较小。结论甘麦大枣汤可以有效改善SHR大鼠关于ADHD的核心症状,上调DRD1、DRD2表达的同时影响肠道菌群的分布。Objective To study the effects of Ganmai Dazao Decoction on behavioral changes, the expression of dopamine receptors DRD1 and DRD2 in the prefrontal cortex and the distribution of intestinal microflora in SHR rats, a model animal of ADHD.Methods SHR rats were randomly divided into Ganmai Dazao Decoction group, Ritalin group,model group, with 8 rats in each group. Another 8 WKY rats were set as the control group. After 7 days of adaptive feeding, each group of rats was gavaged for 21 days, and the backward behavior period was 6 days. Morris water maze test was conducted to evaluate the effects of drugs on learning ability, impulsivity and hyperactivity of SHR rats. Then,Western blot and 16S high-throughput sequencing were used to detect the effect of the drug on the distribution of intestinal flora and prefrontal cortex in SHR rats.Results Compared with the model group, the average latency of the Ganmai Dazao Decoction group and the Ritalin group was shortened, the residence time in the target quadrant was prolonged, the number of crossing platforms was increased, the average speed was slowed down, and the total distance was shortened. Compared with the model group, the protein and mRNA expression levels of DRD1 and DRD2 in the Ganmai Dazao Decoction group and the Ritalin group were significantly increased. The 16S high-throughput sequencing results showed that there were large differences in fecal species diversity between the blank control group and the other three groups;fecal species diversity existed between the model group and Ganmai Dazao Decoction group, and between the model group and Ritalin group. The differences in fecal species diversity between Ganmai Dazao Decoction group and Ritalin group were small. Conclusion Ganmai Dazao Decoction can effectively improve the core symptoms of ADHD in SHR rats, up-regulate the expression of DRD1 and DRD2, and affect the distribution of intestinal flora.

关 键 词：甘麦大枣汤 注意缺陷多动障碍 肠道菌群 

分 类 号：R285[医药卫生—中药学]