Abstract:

To investigate the expressions of βamyloid (Aβ), amyloid precursor protein (APP) and its metabolismrelated enzymes, and to explore the effect of pioglitazone (PIO) intervention in the brain of insulin resistance rats.  MethodsOf 45 Wistar male rats, 10 were randomly chosen as the control group (NC group), and the others were given 10% fructose for 4 weeks to develop the insulin resistance (IR) model. 26 IR rats were randomly divided into the IR group(n=13) and the PIO group (n=13). The PIO group was given pioglitazone(10?mg·kg-1·d-1 by gavage for 12 weeks, and the IR and NC groups were given an identical volume of physiological saline. Immunohistochemistry and Western blotting were employed to examine the level of Aβ42 in the hippocampus and the changes of APP, βsecretase (BACE1) andγsecretase (PS1) in the brain tissue.  ResultsImmunohistochemistry results indicated that the optical density of Aβ42 in the hippocampus of the IR and PIO groups was significantly higher than that of the NC group, and was lower in the PIO group than that of the IR group(P＜0.01). Western blotting showed that APP, BACE1 and PS1 levels in the rat brain were elevated in the IR and PIO groups compared with that in the normal controls，and the concentration in the PIO group was lower than that of the IR group (P＜0.05). ConclusionInsulin resistance promotes Aβ42 by upregulating the activities of BACE1, PS1 and pioglitazone inhibits the activities of BACE1 and PS1 to decrease the expression of Aβ42.

Key words: Insulin resistance； Alzheimer′s disease； Pioglitazone