Michael Shiju Thomas, Ganesh Rajesh Nachiappa, Viswanathan Pragasam
Renal Research Lab, Center for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, India.
Indian J Exp Biol. 2012 Dec;50(12):867-74.
This study was designed to check whether insulin supplementation is crucial for inducing diabetic nephropathy (DNP) in Wistar rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin. The urinary biochemical parameters such as albumin, creatinine and urea nitrogen were monitored every two weeks. The histological changes in the kidney were observed at the end of both fifth and seventh month. Immunohistochemical analyses of VEGF, ERK-1 and NF-kappaB expression were performed to demonstrate mesangial expansion and glomerulosclerosis, which are the defining histological features of nephropathy. A significant change in the urinary biochemistry was observed in diabetic animals at the end of four months, but the aforementioned quantitative changes were delayed in diabetic animals treated with insulin. At the end of seven months, the diabetic animals showed prominent histological changes such as glomerular basement membrane thickening, nodular glomerulosclerosis and mesangial expansion. However, these changes were not observed in diabetic animals treated with insulin even at the end of the study. From the results, it can be concluded that there is no need of insulin supplementation for inducing DNP, when the animals are induced with an optimal dose of 45 mg/kg body weight of streptozotocin.
本研究旨在检验补充胰岛素对于诱导Wistar大鼠发生糖尿病肾病(DNP)是否至关重要。通过单次腹腔注射链脲佐菌素诱导糖尿病。每两周监测尿生化参数,如白蛋白、肌酐和尿素氮。在第五个月和第七个月末观察肾脏的组织学变化。进行VEGF、ERK-1和NF-κB表达的免疫组化分析,以证明系膜扩张和肾小球硬化,这是肾病的典型组织学特征。在四个月末,糖尿病动物的尿生化出现显著变化,但在用胰岛素治疗的糖尿病动物中,上述定量变化出现延迟。在七个月末,糖尿病动物出现明显的组织学变化,如肾小球基底膜增厚、结节性肾小球硬化和系膜扩张。然而,即使在研究结束时,在用胰岛素治疗的糖尿病动物中也未观察到这些变化。从结果可以得出结论,当以45mg/kg体重的最佳剂量链脲佐菌素诱导动物时,诱导DNP无需补充胰岛素。