AdipoRon对2型糖尿病小鼠肾脏损伤的干预作用

目的：研究脂联素受体激动剂（AdipoRon）对2型糖尿病小鼠肾脏损伤的干预作用。方法：将40只SPF级雄性C57/BL6小鼠随机分为正常对照组（n=10）和实验组（n=30）：实验组给予高糖、高脂饲料喂养，联合腹腔注射小剂量链脲佐菌素（STZ）建立2型糖尿病（T2DM）小鼠模型，再随机分为3组（n=10）：模型对照（DM）组、低剂量AdipoRon治疗（DM+L）组及高剂量AdipoRon治疗（DM+H）组。检测血清中葡萄糖含量的变化；采用酶联免疫法检测小鼠血清中胰岛素受体（INSR）、胰岛素受体底物-1（IRS-1）以及肿瘤坏死因子-α（TNF-α）的蛋白质含量；HE染色镜下观察肾组织形态学变化；实时荧光定量PCR法检测肾组织胰岛素促进因子-1（PDX-1）和胰岛素（insulin）mRNA的表达；Western blot检测肾组织内磷酸化胰岛素受体底物-1（p-IRS-1）蛋白质；ELISA试剂盒检测小鼠血胰岛素含量。结果：病理学检查表明，AdipoRon可减轻2型糖尿病所致小鼠肾脏损伤。与DM组小鼠比较，DM+H组和DM+L组小鼠血糖、TNF-α水平均显著降低（P<0.05），INSR、IRS-1和p-IRS-1表达显著上升，PDX-1和insulin mRNA表达显著上升（P<0.05，P<0.01）。结论：给予AdipoRon治疗的小鼠血糖和血清TNF-α水平显著降低，INSR，IRS-1和p-IRS-1蛋白质含量，PDX-1和insulin mRNA表达均显著上升，表明AdipoRon对2型糖尿病小鼠肾脏损伤有一定的干预作用。

The intervention effects of AdipoRon on renal injury in type 2 diabetic mice

Objective: To study the effects of adiponin receptor agonist (AdipoRon) on renal injury in type 2 diabetic mice. Methods: The experiment was carried out on 40 SPF C57/BL6 male mice and they were randomly divided into normal control group (n=10) and experimental group (n=30). Mice in experimental group were given with high sugar and high fat feed in combination with only an intraperitoneal injection of small dose of streptozotocin to build the model of type 2 diabetes (T2DM), which were randomly divided into three groups, model control group (DM), low dose AdipoRon group (DM + L) and high dose AdipoRon group (DM+H)(n=10). Then the change of blood glucose was detected. The serum levels of insulin receptor (INSR), insulin receptor substrate-1 (IRS-1) and tumor necrosis factor-α (TNF-α) in mice were measured by ELASA. Pathological changes of renal tissues were observed with a light microscope after HE staining. The expressions of pancreatic duodenal homebox-1 (PDX-1) and insulin mRNA in renal tissues were detected by RT-PCR. The content of phosphated insulin receptor substrate-1 (p-IRS-1) protein in the kidney was determined by Western blot. Results: Compared with DM mice, blood glucose and TNF-α levels in DM + H mice and DM + L mice were significantly reduced (P<0.05), while the expressions of INSR,IRS-1 and the content of p-IRS-1 were increased markedly(P<0.05), and the expressions of PDX-1 and insulin mRNA in renal tissue were increased significantly(P<0.05, P<0.01). Conclusion: Mice treated with AdipoRon have lower blood glucose and TNF-α levels, and higher protein expression levels of INSR, IRS-1, and higher mRNA expression levels of PDX-1 and insulin, and the content of p-IRS-1. All of these indicate that AdipoRon has a certain effects on renal injury in type 2 diabetic mice.