六味安神汤对失眠小鼠脑组织不同区域单胺类神经递质水平的影响  

Effects of Liuwei Anshen Decoction on the levels of monoamin neurotransmitters in different brain regions of insomnia mice

作　　者：李玉洁[1] 彭慧霞 夏璐瑶 张亦弛 熊阳洋 麻蒙凡 刘庆庆 高航 杨丽萍[1] 侯俊林[1] LI Yu-jie;PENG Hui-xia;XIA Lu-yao;ZHANG Yi-chi;XIONG Yang-yang;MA Meng-fan;LIU Qing-qing;GAO Hang;YANG Li-ping;HOU Jun-lin(Medicine School,Henan University of Chinese Medicine,Zhengzhou 450046,China;First Clinical Medical School,Henan University of Chinese Medicine,Zhengzhou 450046,China;Shuren School,Southern University of Science and Technology,Shenzhen 518055,China)

机构地区：[1]河南中医药大学医学院,郑州450046 [2]河南中医药大学第一临床医学院,郑州450046 [3]南方科技大学树仁书院,深圳518055

出　　处：《中华中医药杂志》2022年第9期5323-5328,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81973596,No.81373790);河南省科技攻关计划项目(No.212102310341)。

摘　　要：目的:探讨六味安神汤对失眠小鼠模型脑组织不同区域单胺类神经递质的影响。方法:采用腹腔注射对氯苯丙氨酸(PCPA)300 mg/kg,连续3 d,建立小鼠失眠模型。建模后,正常组、模型组灌胃0.9%氯化钠溶液10 mL/kg;阳性组灌胃地西泮(1 mg/kg);六味安神汤高、低剂量组分别灌胃41.6、20.8 g/kg六味安神汤水煎液,连续7 d。给药后6 d,检测各组小鼠的睡眠持续时间和易激惹程度;末次给药1 h后,处死小鼠,分离皮质、下丘脑、海马体,采用HPLC法检测皮质、海马及下丘脑5-羟色胺(5-HT)、多巴胺(DA)、肾上腺素(EP)、去甲肾上腺素(NE)、5-羟吲哚乙酸(5-HIAA)、高香草酸(HVA)、左旋多巴(L-DOPA)和3,4二羟基苯乙酸(DOPAC)8种单胺类神经递质的表达水平。并观察皮质及海马区组织病理学改变。结果:与模型组比较,六味安神汤各剂量组小鼠的睡眠持续时间均显著增加(P<0.01),六味安神汤各剂量组易激惹评分显著降低(P<0.01)。此外,六味安神汤高剂量组小鼠皮质DA及其前提物质L-DOPA水平,以及5-HT水平显著升高(P<0.01),海马区NE水平显著降低(P<0.05),5-HT及DOPAC水平显著升高(P<0.05,P<0.01);但下丘脑区DA及NE水平均显著降低(P<0.01,P<0.05)。病理学检测结果显示,六味安神汤各剂量组及地西泮组小鼠海马神经元细胞数量增加。结论:六味安神汤可以增加小鼠睡眠持续时间,降低易激惹程度评分,其作用机制可能与调节脑组织各部位神经递质分泌紊乱有关。Objective: To investigate the effect of Liuwei Anshen Decoction on the levels of monoamine neurotransmitters in different regions of brain tissue of insomnia mice. Methods: The insomnia mice model was induced by intraperitoneal injection of PCPA 300 mg/kg for 3 days. After the establishment of insomnia model, the mice in normal and model group were oral administrated with 0.9% sodium chloride solution 10 mL/kg;the positive group, and the high-dose and low-dose of Liuwei Anshen Decoction groups were oral administrated with diazepam 1mg/kg, Liuwei Anshen Decoction 41.6g/kg and 20.8 g/kg, respectively, for 7 days. After 6 days administration, the sleep duration and the irritability of mice were detected. And 1 h after the last administration, the mice were sacrificed, and the cortex, hypothalamus and hippocampus were separated. The levels of serotonin(5-HT), dopandne(DA), epinephrine(EP), norepinephrine(NE), 5-hydroxyindole acetic acid(5-HIAA), high vanillic acid(HVA), levodopa(L-DOPA), and 3,4-Dihydroxyphenylacetic acid(DOPAC) were determined by high performance liquid chromatography. In addition, histopathological changes were observed by HE staining. Results: Compared with the model group, the sleep duration of mice in high-and low-dose of Liuwei Anshen Decoction groups were significantly increased(P<0.01), and the irritability score of mice in each-dose of Liuwei Anshen Decoction group was significantly decreased(P<0.01);In addition, the levels of DA, L-DOPA, and 5-HT were significantly increased in cortex of mice in high-dose of Liuwei Anshen Decoction group(P<0.01), meanwhile, the level of NE was significantly decreased(P<0.05), and the levels of 5-HT and DOPAC were significantly increased in hippocampus of mice(P<0.05, P<0.01);but the levels of DA and NE in hypothalamus were significantly decreased(P<0.01, P<0.05). In the meantime, the histopathological results showed that the numbers of the neurons in hippocampus of the mice were increased significantly in Liuwei Anshen Decoction groups and diazepam group. C

关 键 词：六味安神汤 失眠 单胺类神经递质 皮质 下丘脑 海马体 

分 类 号：R285.5[医药卫生—中药学]