The modeling of acute hyperglycemia in conscious rats and the kidney damaging characteristics and mechanism

Abstract

Objective To establish the modeling of acute hyperglycemia, observe the characteristics of acute hyperglycemia induced kidney damages, and to explore its possible mechanisms. Methods Sprague-Dawley rats were divided into hyperglycemia group and control group according to the random number table, and underwent catheterization through jugular vein before acute hyperglycemic clamp to establish the modeling of acute hyperglycemia. Rats in hyperglycemia group were infused with 50% glucose solution at the 5th day after the surgery to maintain the blood glucose between 16 and 18 mmol/L, and rats in control group were infused with normal saline for 6 hours. Then 24-hour urine was collected and the rats were killed. Renal structure alterations were observed under optical and transmission electron microscope, renal injury were evaluated by detecting renal function, urinary microalbumin (UMA) and kidney injury molecule-1(KIM-1), and oxidative stress activation were assessed by detecting superoxide dismutase(SOD), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine(8-OHdG). Results The renal morphologic and functional injuries were found in hyperglycemia group, and severe damages were found in tubular epithelial cells including the enlargement of epithelial cells, the swelling and disarrangment of mitochondria of epithelial cells. Compared with control group, UMA, KIM-1, and neutrophil gelatinase-associated lipocalin (NGAL) level were increased significantly in hyperglycemia group (t=-2.969, -2.220, -2.791, all P<0.05). Moreover, compared with control group, serum and renal SOD activity were decreased (t=2.537, 2.599, all P<0.05), while serum MDA, renal MDA and urinary 8-OHdG level were increased significantly in hyperglycemia group(t=-2.532, -2.600, -2.968, all P<0.05). Conclusions The acute hyperglycemia model in healthy rats are set up successfully. Acute hyperglycemia causes significant damages of renal morphology and functions, especially to tubular epithelial cells, mitochondria injuries and oxidative stress activation may play important roles in acute hyperglycemia induced kidney injuries. Key words: Hyperglycemic toxicity; Renal tubule; Oxidative stress