何首乌提取物对注意缺陷多动障碍模型大鼠BDNF/TrkB及其下游信号通路的影响  

Effects of Polygonum Multiflorum Thunb Extract on BDNF/TrkB and Its Downstream Signaling Pathways in Rat Model of Attention Deficit Hyperactivity Disorder

作　　者：冯容 孙继超 张碧霞 朱万青 谢胜[1] 艾军[2] FENG Rong;SUN Jichao;ZHANG Bixia;ZHU Wanqing;XIE Sheng;AI Jun(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;Guangxi University of Chinese Medicine,Nanning 530299,China)

机构地区：[1]广西中医药大学第一附属医院,南宁530023 [2]广西中医药大学,南宁530299

出　　处：《中国中医基础医学杂志》2024年第8期1356-1361,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金青年项目(81804146);国家自然科学基金地区项目(82260953);广西自然科学基金青年项目(2017JJB140344y);广西自然科学基金面上项目(2020JJA140275);2022年研究生教育创新计划项目(YCBXJ2022001)。

摘　　要：目的观察何首乌提取物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。方法选择自发性高血压大鼠(spontaneously hypertensive rat,SHR)为ADHD模型,随机分为模型组、托莫西汀组(4.5 mg/kg),何首乌低(0.54 g/kg)、中(1.08 g/kg)、高(2.16 g/kg)剂量组,另设Wistar京都大鼠为正常组,每组10只。各组大鼠每日给予相应药物灌胃,4周后观察各组大鼠行为学,ELISA法检测前额叶皮质中二十二碳六烯酸(docosahexaenoic acid,DHA)含量,Western blot和RT-qPCR法检测前额叶皮质和海马组织中脑源性神经营养因子(brain derived neurotrophic factor,BDNF)/酪氨酸蛋白激酶受体B(tyrosine kinase receptor B,TrkB)及其下游信号通路中生长因子受体结合蛋白2(growth factor receptor-bound protein 2,Grb2)、肌肉RAS癌基因(muscle RAS oncogene,Ras)3的表达水平。结果托莫西汀和何首乌均能有效控制SHR大鼠多动、冲动行为。与正常组比较,模型组大鼠前额叶皮质中DHA含量降低(P<0.05),BDNF、TrkB、Grb2、Ras3蛋白和mRNA表达明显降低(P<0.01),海马中BDNF、TrkB、Grb2、Ras3蛋白和BDNF、Ras3 mRNA表达明显下调(P<0.05)。给药4周后,在前额叶皮质中,何首乌低、中、高剂量组大鼠DHA含量均显著升高(P<0.01),BDNF、TrkB、Grb2、Ras3的mRNA表达水平均显著上升(P<0.01),何首乌低、中剂量组大鼠BDNF、TrkB、Grb2蛋白,高剂量组大鼠BDNF、Grb2、Ras3蛋白表达水平均显著上升(P<0.05);在海马中,何首乌高剂量组大鼠BDNF、TrkB、Grb2、Ras3蛋白和mRNA表达均明显增加(P<0.05)。结论何首乌提取物能够明显改善SHR多动、冲动行为,其机制可能与调节BDNF/TrkB及其下游信号通路有关。Objective To observe the effect of Polygonum Multiflorum Thunb extract(PME)on attention deficit hyperactivity disorder(ADHD)model rats and the related mechanism.Methods Spontaneously hypertension rat(SHR)were used as ADHD model.SHR rats were randomly divided into model group,tomoxetine treated group(4.5 mg/kg),PME low-(0.54 g/kg),medium-(1.08 g/kg),and high-(2.16 g/kg)dose group,Wistar-Kyoto(WKY)rats were selected as normal control group(n=10).Drugs were given twice a day for 4 weeks.After 4 weeks of intervention,docosahexaenoic acid(DHA)contents in prefrontal cortex were determined by ELISA kits.Western blot and RT-qPCR were used to detect associated factors in brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrkB)and its downstream signaling pathway,such as Gr62 and Ras3.Results Both tomoxetine and PME could ameliorate the spontaneous and impulsive behaviors of SHR rats.Compared with the normal group,the model group shared decreased DHA levels(P<0.05),the mRNA and protein expressions of BDNF,TrkB,Grb2,Ras3 were significantly down-regulated(P<0.01)in the prefrontal cortex,the expressions of protein of BDNF,TrkB,Grb2,Ras3 and the mRNA of BDNF、Ras3 were significantly down-regulated(P<0.05)in the hippocampus.After 4 weeks of intervention,in the prefrontal cortex,the DHA levels and the mRNA expressions of BDNF,TrkB,Grb2,Ras3 in PME low、medium and high-dose groups were significantly up-regulated(P<0.01),the expressions of protein of BDNF、TrkB、Grb2 in PME low,medium-dose groups and the expressions of protein of BDNF,Grb2,and Ras3 in PME high-dose group were significantly up-regulated(P<0.05).In the hippocampus,the mRNA and protein expressions of BDNF,TrkB,Grb2,and Ras3 in PME high-dose group were significantly up-regulated(P<0.05).Conclusion PME may have a role in improving the spontaneous and impulsive behaviors in SHR,which may be contributed to the regulation of BDNF/TrkB mediated downstream signaling pathways.

关 键 词：何首乌提取物 注意缺陷多动障碍 脑源性神经营养因子 酪氨酸蛋白激酶受体B 

分 类 号：R259[医药卫生—中西医结合] R285.5[医药卫生—中医内科学]