吡格列酮对肥胖2型糖尿病大鼠胰岛素抵抗、炎症和脂肪缺氧状态的影响

摘要

目的 探讨吡格列酮(PGZ)对肥胖2型糖尿病(T2DM)大鼠胰岛素抵抗、炎症和脂肪缺氧状态的影响.方法 将40只Zucker糖尿病肥胖模型大鼠随机分为PGZ模型组、生理盐水模型组、PGZ对照组和生理盐水对照组各10只.对所有大鼠进行高脂喂养以诱导肥胖和高糖血症.造模成功后,对PGZ模型组和PGZ对照组大鼠进行PGZ灌胃,其余两组给予相同体积的生理盐水灌胃,共10周.于造模前、造模成功后及干预10周后行外周血单核细胞亚群分析;干预10周后行腹腔葡萄糖耐量试验和胰岛素耐量试验,并麻醉处死动物,取肾周脂肪检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、缺氧诱导因子1-α(HIF1-α)mRNA表达水平.结果 干预10周后,生理盐水模型组的抑炎型单核细胞占单核细胞总数的比例低于其他3组(P<0.05),血糖及胰岛素水平、TNF-α、IL-6及HIF1-α mRNA相对表达水平均高于其他3组(P<0.05),而PGZ模型组与两个对照组的TNF-α、IL-6及HIF1-α mRNA相对表达水平、抑炎型单核细胞比例比较,差异均无统计学意义(P>0.05).结论 PGZ可改善肥胖T2DM大鼠胰岛素抵抗,同时也能缓解脂肪组织炎症与缺氧情况.%Objective To investigate the effects of pioglitazone(PGZ) on insulin resistance,inflammation and hypoxia of adipose tissues in obesity rats with type 2 diabetes mellitus(T2DM ).Methods Forty Zucker diabetic obesity rats were randomly divided into PGZ model group,normal saline model group,PGZ control group and normal saline control group,with 10 rats in each group.Obesity and hyperglycemia were induced by high-fat diet in all rats.After successful modeling,intragastric administration of PGZ was performed in the rats of the PGZ model group and PGZ control group for 10 weeks,and intragastric administration of normal saline in the rats of the normal saline model group and normal saline control group for 10 weeks.The analysis on peripheral blood monocyte subsets was performed before modeling,after successful modeling and after 10 weeks of administration.After 10 weeks of administration,intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were conducted.Then the anesthetic rats were killed,and the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and hypoxia-related hypoxia-inducible factor 1-alpha(HIF1-α) mRNAs were detected in the perirenal adipose tissues.Results After 10 weeks of administration,the ratio of anti-inflammatory monocytes to total monocyte count in the normal saline model group was lower than that in the other three groups(P<0.05),the glucose and insulin levels and the relative expression levels of TNF-α,IL-6 and HIF1-α mRNAs in the normal saline model group were higher than those in the other three groups(P<0.05).But there were no significant differences in the relative expression levels of TNF-α,IL-6 and HIF1-α mRNAs,or the ratio of anti-inflammatory monocytes among the PGZ model group and the two control groups(P>0.05).Conclusion PGZ can improve the insulin resistance of obesity rats with T2DM,and also can alleviate the inflammation and hypoxia of adipose tissues.