OBJECTIVETo investigate the relation between diabetic nephropathy and nuclear factor-kappaB (NF-kappaB) expression, and observe the effect of reduced glutathione sodium (GSH) on NF-kappaB activation and in prevention of diabetic nephropathy.

METHODSSeventy male Sprague-Dawley rats weighing 200-/+25 g were randomized into control group (10 rats) and diabetic group (60 rats, subgrouped into 1 month, 3 months, 6 months and their corresponding intervention subgroups, each consisting of 10 rats). The rats in the 6 diabetic groups were subjected to intraperitoneal injection of streptozotocin, and those in the control group received injection with 0.1 mmol/L citric acid buffer solution of the same volume. The diabetic models were affirmed upon a fasting blood glucose >or=16.5 mmol/L 3 days after the injection. The intervention groups were injected intraperitoneally with GSH (10 mg/100 g) once daily. Fasting blood glucose and body weight were measured every week. The rats were executed at the end of 1, 3, and 6 months respectively and the nucleoproteins were extracted from the renal specimen. NF-kappaB was measured using electrophoretic mobility shift assay (EMSA) after labeling with isotope probe, and the gray scale of the electrophoretic bands was analyzed.

RESULTSEMSA optical density analysis of electrophoretic bands showed that NF-kappaB expression increased in each diabetic groups in comparison with the control group (P<0.05), and NF-kappaB level rose proportionally with the disease course of 1 month, 3 months and 6 months. The activity of NF-kappaB decreased in the intervention groups as compared with the corresponding untreated groups (P<0.05).

CONCLUSIONThe activation of NF-kappaB plays a role in the onset and development of diabetes. NF-kappaB inhibition and containment of inflammation might be one of the mechanisms of GSH treatment for diabetes.