The Research Of MTOR And Tau Phosphorylated Protein In Hippocampal Tissue Of Type2Diabetes And Alzheimer’s Disease Rats

Objective:1. To observe levels of mTOR and hyperphosphorylation of tau protein ofhippocampal tissue in the type2diabetes mellitus and Alzheimer’s disease rats.2. To discuss the role of mTOR in the pathogenesis of increased risk of type2diabetes mellitus combined with Alzheimer’s disease.Methods:Sprague-Dawley maleness rats whose body weight was （200±20）g wererandomly divided into four groups:control group, type2diabetes mellitus modelgroup (T2DM group), Alzheimer’s disease model group (ADgroup) and type2diabetes mellitus combined with Alzheimer’s disease model group (T2DM+ADgroup). Rats in T2DM group were established by high-glucose-high-fat diet andstreptozotocin. The fasting blood glucose levels were assayed. The fasting blood-glucose for successful standard of type2diabetes model is16.7mmol/L. Rats in ADgroup were established by bilateral microinjection of Aβ1-40into hippocampus.Morris water maze test was used to judge that the model succeeds or not.1. Blood gathered from inferior vena cava was used to detect FBG,TC,TG.2. The behavior changes were tested by Morris water maze.3. The expression of mTOR and hyperphosphorylation of tau protein were dete-cted by immunohistochemical staining．4. The levels of mTORmRNA and total tau protein mRNA were detected byRT-PCR.Results:1. Biochemistry: compared with control group and AD group, levels of FBG,TCand TG of T2DM group and T2DM+AD group were enhanced (P<0.01). There wasno significant difference between control group and ADgroup(P>0.05). It’s level ofT2DM+AD group was higher than T2DM group (P<0.05).2. Morris water maze test: compared with control group and T2DM group, thelearning and memory abilities of AD group and T2DM+AD group were weakened significantly (P<0.01). There was significant difference between control group andT2DM group(P<0.01). Significant difference was also existed between AD group andT2DM+AD group (P<0.05).3. Immunohistochemical staining: compared with control group and AD group,the level of mTOR in hippocampal tissue of T2DM group and T2DM+AD group wassignificantly increased(P<0.05). There was no significant difference between controlgroup and AD group(P>0.05). It’s level of T2DM+AD group was higher than T2DMgroup (P<0.01).Compared with control group and T2DM group, the level of hyperphosphory-lation of tau protein in hippocampal tissue of AD group and T2DM+AD group wassignificantly increased (P<0.01). There was no significant difference between controlgroup and T2DM group(P>0.05). It’s level of T2DM+AD group was higher than ADgroup (P<0.01).4. RT-PCR: compared with control group and AD group, the expression ofmTORmRNA in hippocampal tissue of T2DM group and T2DM+AD group wassignificantly increased(P<0.05). There was no significant difference between controlgroup and AD group(P>0.05). It’s level of T2DM+AD group was higher than T2DMgroup (P<0.01).Compared with control group and T2DM group, the expression of total tauproteinmRNA in hippocampal tissue of AD group and T2DM+AD group wassignificantly increased (P<0.01). There was no significant difference between controlgroup and T2DM group(P>0.05). It’s level of T2DM+AD group was higher than ADgroup (P<0.01).Conclusion:T2DM cause the excessive activation of mTOR in the hippocampal tissue, whichmay through the damaging of insulin signaling. The excessive activation of mTORwill increase the dgree of hyperphosphorylation of tau，which may promote theoccurrence of AD.