L-亮氨酸改善高原记忆损伤作用  

Improving Effect of L-leucine on Memory Impairment in Plateau

作　　者：周保柱[1,2] 栾飞[2,3] 李茂星[1,2,3] 张泉龙[2] 贾正平[1,2] 

机构地区：[1]兰州大学药学院,兰州730000 [2]兰州军区兰州总医院全军高原环境损伤防治重点实验室国家中医药管理局临床中药学重点学科,兰州730050 [3]甘肃中医药大学药学院,兰州730000

出　　处：《医药导报》2016年第3期237-241,共5页Herald of Medicine

基　　金：全军后勤科研"十二五"计划重点项目(BWS12J012);甘肃省青年科技基金计划(1208RJYA077)

摘　　要：目的探讨L-亮氨酸对高原记忆损伤的改善作用及其机制。方法通过八臂迷宫筛选雄性昆明种小鼠50只,随机分为常氧对照组(NC组),模型对照组(Model组),L-亮氨酸小、中、大剂量组。L-亮氨酸小、中、大剂量组分别按0.473,0.945,1.89 g·kg-1剂量灌胃给予L-亮氨酸,NC组和Model组给予等体积纯化水。均给药1周。给药第4天,将Model组和L-亮氨酸小、中、大剂量组置于大型低压氧舱模拟高原低压低氧环境(海拔7 500 m,3 d)。采用八臂迷宫测试其空间学习记忆能力;干/湿比重法测定各组脑组织含水量变化;苏木精-伊红(HE)染色观察海马CA1区细胞形态变化;SYBR Green实时定量PCR检测海马组织mTOR、P70S6K和4E-BP1 mRNA表达。结果与NC组比较,Model组参考记忆错误(RME)、错误总数(TE)及测试时间(TT)均显著增加(P<0.05),脑含水量显著升高(P<0.01),海马CA1区神经元损伤加重,mTOR和P70S6K mRNA表达显著降低(P<0.05)。与Model组比较,L-亮氨酸小、中剂量组工作记忆错误(WME)、RME、TE、TT、脑含水量和4E-BP1 mRNA表达均降低,P70S6K mRNA表达增加;L-亮氨酸大剂量组WME和TE均显著降低(P<0.05),脑含水量显著降低(P<0.01),P70S6K mRNA表达显著增加(P<0.05)。L-亮氨酸小、中、大剂量组海马CA1区神经元损伤明显减轻。结论 L-亮氨酸对高原记忆损伤有改善作用,其机制可能通过激活mTOR及其下游底物(4E-BP1和P70S6K)发挥作用。Objective To explore the improving effect of L-leucine on memory impairment in plateau and the mecha-nism. Methods After successfully trained in the 8-arm radial maze,50 male Kunming mice were selected and randomly divid-ed into normoxic control group （NC group）,model group,and L-leucine （low,medium and high dose） groups.Animals in L-leu-cine groups were intragastrically given 0.473 g-kg-1 ,0.945 g-kg-1 and 1.89 g-kg-1 L-leucine for 7 days and those in NC and model control groups were administered the same volume of purified water for the same period of time.At the 4th day of the treat-ment,the mice in the model control group and L-leucine groups were placed in a large low-pressure and low-oxygen chamber to simulate low-pressure hypoxic environment of the plateau （7 500 m,3 d）.The 8-arm radial maze was used to measure the spatial learning and memory ability of mice and dry-wet method to measure the water content of brain tissue.HE staining was employed to observe the cell morphological changes in CA1 region of the hippocampus.The expression levels of mTOR,P70S6K and 4E-BP1 mRNA in the hippocampus were detected by SYBR Green real-time PCR. Results The reference memory error （ RME） ,total error （ TE） ,testing time （ TT） ,and water content of brain tissue were significantly increased,the neuron injury was exacerbated in CA1 region of the hippocampus,and the expression levels of mTOR and P70S6K mRNA were markedly decreased in model control group when compared with those in NC group （P〈0.05 or P〈0.01）.These indexes,however,were significantly improved in L-leu-cine groups,especially in high-dose group. Conclusion L-leucine can improve memory impairment in plateau,and the mecha-nism may involve the activation of mTOR and its downstream substrates （4E-BP1 and P70S6K）.

关 键 词：L-亮氨酸 雷帕霉素靶蛋白 4E-BP1 P70S6K 高原记忆损伤 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]