Abstract:

Objective  To explore the level and injury mechanism of advanced glycosylation end products(AGES) in the vascular system of rats with insulin resistance and the protective effects of Pioglitazone. Methods  6-8-week-old Wistar rats were randomly divided into the control group (NC group，  n=10), the insulin resistance group (IR group，  n=13) and the Pioglitazone group (PIO group，  n=13).The latter two groups were developed into the insulin resistance model. The PIO group were given Pioglitazone 10mg/ (kg·d) by gavage for 12 weeks.  Expressions of advanced glycosylation end products were detected by immunofluorescence. The mRNA expression levels of RAGE and NADPH oxidase p47phox were detected by RT-PCR respectively. Immunohistochemistry was performed to detect expression of RAGE and phosphor-NF-Кb protein. Results  Compared with the IR group,  expression of AGEs decreased in PIO group. Expression of AGEs in the two groups was significantly higher than in the NC group. RAGE, NADPH oxidase P47phox, and mRNA expressions in the IR group and the PIO group were significantly higher than that in the NC group(P<0.01).But, in the PIO group  expression of these indicators  decreased in comparison with the IR group (P<0.05).RAGE and phosphor-NF-Кb protein expression in the PIO group were reduced in comparison with the IR group (P<0.05), while in the other two groups, RAGE and phosphor-NF-Кb protein expressions  were significantly stronger than the NC group (P<0.01). Conclusions  Expression of AGEs protein is increased in the vascular system of rats with insulin resistance, which can promote oxidative stress and inflammatory response. Pioglitazone can inhibit  oxidative stress and the inflammatory response by decreasing  expression of AGEs and RAGE and the activation of NF-Кb to reverse the vascular injury.

Key words: Insulin resistance; Advanced glycosylation end products; Pioglitazone; Oxidativestress