胰岛素抵抗大鼠血管AGEs水平及其损伤机制和吡格列酮的保护作用

目的  探讨胰岛素抵抗大鼠血管AGEs水平及其损伤机制和吡格列酮的保护作用。方法  选6~8 周龄Wistar大鼠随机分为对照组（NC组，n=10）、胰岛素抵抗组(IR组，n=13)和吡格列酮组(PIO组，n=13)。后两组建立胰岛素抵抗模型，模型成功后PIO组给予吡格列酮［10mg/(kg·d)］干预，12周后采用免疫荧光技术检测血管壁AGEs表达；应用RT-PCR法检测RAGE 、NADPH氧化酶 p47phox mRNA 的表达；免疫组织化学技术检测RAGE、磷酸化NF-Кb蛋白的表达。结果  与IR组比较，PIO组AGEs的表达减弱，而两组明显高于NC组；IR组和PIO组RAGE、NADPH氧化酶P47phox mRNA表达较NC组明显升高(P< 0.01)，而PIO组上述指标表达较IR组减弱（P<0.05）；PIO组RAGE、磷酸化NF-Кb蛋白表达较IR组减弱（P<0.05），但两组均明显强于NC组（P<0.01）。结论  胰岛素抵抗大鼠血管AGEs及RAGE表达增多，继而促进氧化应激及炎症反应导致血管损伤；吡格列酮能通过减少AGEs、RAGE生成而抑制氧化应激及炎症反应，改善血管损伤。

Level and injury mechanism of AGEs in the vascular system of insulin resistance rats and protective effects of Pioglitazone

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.