硫化氢对糖尿病性认知障碍的拮抗作用及其海马warburg效应依赖机制

H2S是一新颖的促学习记忆信号分子，探讨其抗糖尿病性认知障碍(DACD)作用具有重要意义。warburg效应对学习记忆具有调节作用。本项目拟在糖尿病大鼠模型上，首先明确H2S的抗DACD作用，然后在揭示海马warburg效应是DACD有效防治靶点的基础上，探讨H2S对海马warburg效应的增强作用以及阻断海马warburg效应对H2S抗DACD的逆转作用，以阐明H2S抗DACD机制在于增强海马warburg效应。探讨H2S对海马warburg效应关键酶PDK-1和LDHA的硫巯基化作用以及阻断硫巯基化对H2S增强海马warburg效应的逆转作用，以阐明H2S增强海马warburg效应的分子机制在于硫巯基化PDK-1和LDHA。项目的开展，将明确H2S的抗DACD作用及其海马warburg效应增强机制，为H2S的生物学作用增添新认识，为DACD的防治提供新思路。

It is important to explore the therapeutic action of H2S, a novel signal molecule that play an important role in learning and memory, in diabetes-associated cognitive dysfunction (DACD). The warburg effect in brain has a regulatory role in learning and memory. In this project, we will use the animal models of diabetes mellitus first to confirm that H2S can prevent DACD and clear that the warburg effect in hippocampus is a effective target for prevention of DACD, and then to reveal that the mechanism underlying the antagonistic action of H2S in DACD is to enhance the warburg effect in hippocampus by investigating whether H2S can enhance the warburg effect in hippocampus and whether inhibition of hippocampal warburg effect can reverse the antagonistic effect of H2S on DACD. To explore that the mechanism underlying H2S-induced enhancement in hippocampal warburg effect lies in S-sulfhydration of PDK-1 and LDHA, which are the key enzymes in the warburg effect, we will investigate whether H2S can S-sulfhydrate PDK-1 and LDHA and whether suppression in S-sulfhydration of PDK-1 and LDHA can reverse H2S-enhanced warburg effect. This project will confirm the therapeutic function of H2S in DACD and its hippocampus warburg effect-depended mechanism, add new understanding for the biology function of H2S, and provide a novel therapeutic approach for the treatment of DACD.