Improving Effect of L-leucine on Memory Impairment in Plateau / 医药导报

ABSTRACT

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).