Research On GSK-3β,Hyperphosphorylated Tau Protein Of Type 2 Diabetic Mellitus And Alzheimer's Disease Rats

Objective : To investigate the relationship between the activity of glycogen synthase kinase-3β(GSK-3β) of Type 2 Diabetic Mellitus Rats and hyperphosphorylated tau proteinMethods:1. Establish model of Type 2 Diabetic Mellitus (T2DM) Rats. Fed by high-fat and high-caloric 3 months then injected a very small dose of streptozotocin (STZ) through intravenous.2. Establish model of Alzheimer's disease (AD) Rats. Okadaic acid (OA) was injected into the hippocampus CA1 region overnight, four times totally.3. Establish model of T2DM and AD Rats. First establish model of T2DM Rats, one week later, establish model of AD Rats.( With the former methods).4. Behavior was tested by the Morris water.5. Research the relationship between GSK-3βand hyperphosphorylated tau protein. The GSK-3βand tau hyperphosphorylation were detected by immunohistochemistry staining.Results:1. Determination of blood glucose: Blood glucose of T2DM group and T2DM+AD group Rats were more than 16.7 mmol/L after injected STZ 72 hours.2. The Morris water maze test manifested:Compared with the control group,T2DM group Rats have have longer escape latency(P<0.01),and significantly reduce the number of sites across(P<0.001),which has the obvious difference; AD group and T2DM+AD group Rats injected with OA have longer escape latency(P<0.001),and significantly reduce the number of sites across(P<0.001),which has the obvious difference; Compared with the AD group,T2DM+AD group Rats have have longer escape latency(P<0.01),and significantly reduce the number of sites across(P<0.001),which has the obvious difference; Compared with the T2DM group, AD group Rats have have longer escape latency(P<0.001),and significantly reduce the number of sites across(P<0.001),which has the obvious difference.3. The activity of GSK-3β: Positive cells could be seen obviously in T2DM+AD group,but rarely in T2DM group. It is obviousely difference (P<0.001).we couldn't see positive cells in control group and AD group.4. The activity of hyperphosphorylated tau protein: Positive cells could be seen in AD and T2DM+AD groups, and the IOD in hippocampus of T2DM+AD group is higher than that of the AD group , it is obvious difference(P<0.05);and yet we couldn't see positive cells in control group and T2DM group.5.Weakly positive cells of GSK-3βcould be seen accidentally in T2DM group rats,but we could not see positive cells of hyperphosphorylated tau protein ; In AD group rats,we couldn't see positive cells of GSK-3β,but could see positive cells of hyperphos- phorylated tau protein ;We could see positive cells of GSK-3βand hyperphosphorylated tau protein in T2DM+AD group rats.Conclusion:1. T2DM Rats were successfully induced by high-fat and high-caloric and a very small dose of STZ through intravenous injection.2. AD Rats were successfully induced by injected OA into the hippocampus CA1 region.3. T2DM and AD Rats not only have the high blood glucose but have the behavioural barriers and hyperphosphorylated tau protein.4. Cognition Ability can be injured by T2DM.5. T2DM maybe could promote tau protein phosphorylated though partly increasing the activity of GSK-3βto promote the formation of AD.