Körner A, Celsi G, Eklöf A C, Linné T, Persson B, Aperia A
Department of Pediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
Diabetologia. 1992 May;35(5):414-8. doi: 10.1007/BF02342436.
The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.
在链脲佐菌素诱导的糖尿病大鼠中研究了醛糖还原酶抑制对肾功能的影响。糖尿病大鼠通过每日胃内灌喂给予索比尼尔(20和50毫克/千克),并与未治疗的糖尿病大鼠和正常大鼠进行比较。对大鼠进行每日血糖控制、胰岛素给药和体重方面的监测。目的是促进身体持续生长,并将血糖浓度维持在约22毫摩尔/升左右,且无大幅的每日波动。在这个成熟的糖尿病模型中观察到的肾功能变化与人类1型(胰岛素依赖型)糖尿病中报道的变化非常相似。索比尼尔治疗完全阻止了肾皮质山梨醇的积累,但并未消除肾脏肿大或超滤压力和肾小球滤过率的增加。在索比尼尔治疗的糖尿病大鼠和未治疗的糖尿病大鼠中,白蛋白排泄增加的程度相同。我们得出结论,葡萄糖向山梨醇的代谢增加并不会导致链脲佐菌素诱导的糖尿病大鼠出现超滤过。