八角枫提取物的神经毒性及对脑组织神经递质的影响  

Neurotoxicity of Alangium chinense and its effect on neurotransmitters in brain tissue

作　　者：练东银 陈颖[1] 李晗 陈腾飞 侯红平 高云航 宋玲 蒲健 张广平[1] 彭博 LIAN Dongyin;CHEN Ying;LI Han;CHEN Tengfei;HOU Hongping;GAO Yunhang;SONG Ling;PU Jian;ZHANG Guangping;PENG Bo(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100020,China;Guizhou Yibai Pharmaceutical Co.LTD,Guiyang 550000,China)

机构地区：[1]中国中医科学院中药研究所,北京100020 [2]贵州益佰制药股份有限公司,贵阳550000

出　　处：《中华中医药杂志》2023年第12期6003-6007,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重点研发计划(No.2018YFC1708100,No.2018YFC1708105)。

摘　　要：目的:研究八角枫提取物的神经毒性作用及对脑组织神经递质的影响。方法:70只小鼠(雌雄各半)随机分为对照组、不同剂量八角枫提取物组(剂量为3、6、12、25、50、100g生药/kg),每组10只,连续灌胃给药2周,每周测量小鼠体质量、24h进食量。给药2周后检测小鼠神经行为学(抓力和自主活动)。采用高效液相色谱-质谱联用(LC-MS/MS)检测小鼠脑组织中神经递质乙酰胆碱(ACh)、去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)、3,4-二羟苯乙酸(DOPAC)、高香草酸(HVA)、5-羟吲哚乙酸(5-HIAA)含量。以酶联免疫吸附(ELISA)法检测小鼠血清神经标志物神经特异性烯醇化酶(NSE)、神经生长因子(NGF)的含量。结果:与对照组比较,八角枫提取物各剂量组小鼠的体质量和进食量无明显变化;八角枫提取物组剂量为6、12、25、50、100g生药/kg时,小鼠的抓力开始显著降低(P<0.05,P<0.01);当八角枫提取物组剂量为25、50、100g生药/kg时,小鼠自主活动中站立次数、运动时间、运动速度、运动路程、总路程、平均速度显著降低,静止时间显著延长(P<0.05,P<0.01);血清中NGF含量减少,NSE含量增加(P<0.05,P<0.01),当八角枫提取物剂量为50、100g生药/kg时,小鼠脑组织中的ACh、NE、DA、5-HT、DOPAC、HVA水平降低,(DOPAC+HVA)/DA比值升高(P<0.05,P<0.01)。结论:八角枫提取物对小鼠具有神经毒性作用,能够影响小鼠的行为学、神经递质水平和血清神经标志物水平。其神经毒性的机制可能与调控胆碱能和单胺类神经递质水平及损伤神经元有关。Objective:To study the neurotoxicity and regulation of neurotransmitters of the extracts of Alangium chinense.Methods:A total of 70 mice(half male and half female)were randomly divided into seven groups with 10 mice in each group and orally irrigated with the distlled water(control group),Alangium chinense(AC group,3,6,12,25,50,100 g crude herbs/kg)oncedaily for 2 weeks.The body weight and 24 h food intake of mice was measured every week.Mice neurobehavioral(grip test and open-field test)were examined two weeks after dosing.The contents of neurotransmitters acetylcholine(ACh),norepinephrine(NE),dopamine(DA),5-hydroxytryptamine(5-HT),(3,4-dihydroxyphenyl)acetic acid(DOPAC),homovanillic acid(HVA)and 5-hydroxyindole acetic acid(5-HIAA)in mouse brain tissue were detected by high performance liquid chromatography-mass spectrometry(LC-MS/MS).The contents of neuron-specific enolase(NSE)and nerve growth factor(NGF)in the serum of mice were detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the control group,there was no significant change in the body weight and food intake of the mice in the Alangium chinense groups;at 6,12,25,50,100 g crude drug/kg of the Alangium chinense groups,the grip strength of the mice was significantly reduced(P<0.05,P<0.01).At a dose of 25,50,100g crude drug/kg in the Alangium chinense groups,total distance traveled,number of rearing,exercise time,exercise speed,exercise distance,and average speed in locomotor activity decreased,the resting time increased(P<0.05,P<0.01);the content of NGF in serum decreased,and the content of NSE increased(P<0.05,P<0.01);the levels of ACh,NE,DA,5-HT,5-HIAA,DOPAC,and HVA in the brain tissue decreased,and the ratios of 5-HIAA/5-HT and(DOPAC+HVA)/DA increased(P<0.05,P<0.01).Conclusion:The extract of Alangium chinense has neurotoxic effect on mice,which can affect the behavior,neurotransmitter levels and serum neuromarker levels of mice.The mechanism of its neurotoxicity may be related to regulating the levels of cholinergic and monoamine ne

关 键 词：八角枫 神经毒性 神经行为学 神经递质 神经标志物 

分 类 号：R285.5[医药卫生—中药学]