毛蕊花苷对高原缺氧小鼠记忆损伤的改善及机制研究
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摘要
目的探讨毛蕊花苷对高原缺氧记忆损伤的改善作用及其可能机制。方法采用八臂迷宫训练小鼠的空间记忆能力,训练成功后随机分为5组:常氧对照组(蒸馏水0.1 ml/10g)、缺氧模型组(蒸馏水0.1 ml/10g)、毛蕊花苷低(50mg/kg)、中(150mg/kg)、高(300mg/kg)剂量组,灌胃给药7d。第4天给药完毕后,除常氧对照组置于饲养室(1 500m)外,剩余4组置于大型低压氧舱模拟高原缺氧环境(7 500m,3d)。行八臂迷宫测试(4 000m),解剖取血浆和脑组织,测定脑组织活性氧(ROS)、血浆和脑组织丙二醛(MDA)、还原型谷胱甘肽(GSH)含量,总超氧化物歧化酶(T-SOD)活力。结果与常氧对照组相比,缺氧模型组八臂迷宫实验各项指标、脑组织ROS、MDA及血浆MDA显著升高,脑组织和血浆GSH含量、T-SOD活力显著降低;与缺氧模型组相比,毛蕊花苷各剂量组八臂迷宫实验各项指标、脑组织ROS、MDA及血浆MDA都呈现不同程度的降低,脑组织和血浆GSH含量、T-SOD活力呈现不同程度的升高。结论毛蕊花苷对高原缺氧记忆损伤有较好的改善作用,可能与其稳定机体抗氧化酶系统的平衡,减轻氧化应激有关。
Objective To investigate the effects and mechanism of verbascoside on hypoxia-induced memory impairment.Methods The eight-arm maze was used to train mice′s spatial memory ability.After successful training,mice were randomly divided into five groups:a normoxic control group(distilled water,0.1ml/10g),hypoxic model group(distilled water,0.1ml/10g),the verbascoside low dose group(50 mg/kg),medium dose group(150 mg/kg),and high dose group(300mg/kg)were administered orally once a day for a total of 7days.After administration on the fourth day,except for the normoxic control group was placed in the animal room(1 500m),the remaining four groups were placed in a large-scale hypobaric chamber to simulate the hypoxic environment of the plateau(7 500 m,3days).Eight-armed maze test(4 000m)was used and the plasma and brain tissues were dissected out and measured for reactive oxygen species(ROS)in the brain,malondialdehyde(MDA),reduced glutathione(GSH)and total superoxide dismutase(T-SOD)activity in plasma and brain.Results Compared with the normoxic control group,the indexes of the eight-armed maze,ROS and MDA in the brain,MDA in the plasma of the hypoxia model group were significantly increased,and the GSH and T-SOD enzyme activities in the brain and plasma were notably decreased.Compared with the hypoxic model group,the indexes of the eight-armed maze,ROS and MDA in the brain,MDA in the plasma in the various groups of verbascoside were reduced more or less,the GSH and T-SOD enzyme activities in the brain and plasma slightly were increased.Conclusion Verbascoside could ameliorate the hypoxic memory impairment at high altitude,which might be related to the stabilization of the body′s antioxidant enzyme system balance and reduce oxidative stress.
Objective To investigate the effects and mechanism of verbascoside on hypoxia-induced memory impairment.Methods The eight-arm maze was used to train mice′s spatial memory ability.After successful training,mice were randomly divided into five groups:a normoxic control group(distilled water,0.1ml/10g),hypoxic model group(distilled water,0.1ml/10g),the verbascoside low dose group(50 mg/kg),medium dose group(150 mg/kg),and high dose group(300mg/kg)were administered orally once a day for a total of 7days.After administration on the fourth day,except for the normoxic control group was placed in the animal room(1 500m),the remaining four groups were placed in a large-scale hypobaric chamber to simulate the hypoxic environment of the plateau(7 500 m,3days).Eight-armed maze test(4 000m)was used and the plasma and brain tissues were dissected out and measured for reactive oxygen species(ROS)in the brain,malondialdehyde(MDA),reduced glutathione(GSH)and total superoxide dismutase(T-SOD)activity in plasma and brain.Results Compared with the normoxic control group,the indexes of the eight-armed maze,ROS and MDA in the brain,MDA in the plasma of the hypoxia model group were significantly increased,and the GSH and T-SOD enzyme activities in the brain and plasma were notably decreased.Compared with the hypoxic model group,the indexes of the eight-armed maze,ROS and MDA in the brain,MDA in the plasma in the various groups of verbascoside were reduced more or less,the GSH and T-SOD enzyme activities in the brain and plasma slightly were increased.Conclusion Verbascoside could ameliorate the hypoxic memory impairment at high altitude,which might be related to the stabilization of the body′s antioxidant enzyme system balance and reduce oxidative stress.
引文
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[2]周保柱,张泉龙,李茂星,等.高原环境对记忆功能影响的研究进展[J].解放军药学学报,2015,31(1):75-79.
[3]CARDINALI A,PATI S,MINERVINI F,et al.Verbascoside,isoverbascoside,and their derivativesrecovered from olive mill wastewater as possible food antioxidants[J].J Agric Food Chem,2012,60(7):1822-1829.
[4]OYOUROU J N,COMBRINCK S,REGNIER T,et al.Purification,stability and antifungal activity of verbascoside from Lippia javanica and Lantana camara leaf extracts[J].Ind Crop Prod,2013,43:820-826.
[5]SPERANZA L,FRANCESCHELLI S,PESCE M,et al.Antiinflammatory effects in THP-1cells treated with verbascoside[J].Phytother Res,2010,24(9):1398-1404.
[6]SONG X,HE J,XU H,et al.The antiviral effects of acteoside and the underlying IFN-γ-inducing action[J].Food Funct,2016,7(7),3017-3030.
[7]ESPOSITO E,DAL TOSO R,PRESSI G,et al.Protective effect of verbascoside in activated C6glioma cells:possible molecular mechanisms[J].Naunyn Schmiedebergs Arch Pharmacol,2010,381(1):93-105.
[8]ZHOU B,LI M,CAO X,et al.Phenylethanoid glycosides of Pedicularis muscicola maxim ameliorate high altitude-induced memory impairment[J].Physiol Behav,2016,157:39-46.
[9]李茂星,周保柱,刘延彤,等.藓生马先蒿苯乙醇苷对高原记忆损伤的改善作用及机制研究[J].中国药学杂志,2016,51(9):703-707.
[10]DE AQUINO LEMOS V,ANTUNES H K,DOS SANTOS RV,et al.High altitude exposure impairs sleep patterns,mood,and cognitive functions[J].Psychophysiology,2012,49(9):1298-1306.