Abstract: To explore the effects of Pioglitazone on cognition function and AGEs-RAGE system in insulin resistant rats. Methods 6-8week Wistar rats were fed with fructose to develop insulin resistant(IR) models for 4 weeks, then IR rat models were randomly divided into the IR group (n=13) and the Pioglitazone (PIO) group (n=13). Rats in the PIO group were given Pioglitazone 10?mg/(kg·d) by gavage for 12 weeks. The cognition ability of rats was assayed with the Morris water maze test. The expressions of advanced glycation end products were determined by immunofluorescence. Western blotting was used to detect the expression of PPARγ, Phospho -NF-κB and RAGE protein. Results① The Morris water maze test showed that escape latency was longer in the IR group and the PIO group than that in the normal control (NC) group (P＜0.01, P＜0.05), and it was shorter in the PIO group compared with the IR group(P＜0.01). ②　The expression of AGEs protein in the IR group and the PIO group was higher than that in the NC group, also it was significantly decreased in the PIO group compared with the IR group. ③　The expressions of RAGE and Phospho-NF-κB protein in the IR and PIO groups were higher than those in the NC group .Compared with the IR group, the expressions of RAGE and Phospho-NF-κB in the PIO group were significantly decreased. The expression of PPARγ protein in the IR and PIO groups was lower than in the NC group（P＜0.05）, however compared with the IR group, the expression of PPARγ in the PIO group was significantly increased（P＜0.05）. ConclusionThe strengthening of the AGEsRAGE system activation is a possible mechanism of brain damage. Pioglitazone therapy can ameliorate cognition function of IR rats which is probably related to its effect on decreasing the AGEs -RAGE system activation.

Key words: Pioglitazone, Insulin resistance, Cognition, Advanced glycation end product