Abstract: Objective　To study the protective effect and its related mechanism of ethanol extract of Chinese propolis (EECP) on kidney of type 1 diabetic rats. Methods　Sixty-eight male SD rats were injected intraperitoneally (IP) with streptozotocin (STZ) once at a dose of 55 mg/kg for type 1 diabetic rat model. After 72 hours, the tail vein blood glucose of rat was detected, and rats with blood glucose ＞ 16.7 mmol/L were used as diabetes models. After the model induction, the type 1 diabetic rats were divided into five groups according to random number table method: model group, 50 mg/kg, 100 mg/kg, 200 mg/kg of EECP groups and metformin (75 mg/kg) group, 10 rats for each group. Another 10 normal rats were taken as the normal group. After 12 weeks, blood glucose, creatinine (Scr), urea nitrogen (BUN), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in each group. HE staining was used to observe renal pathological changes. The protein expressions of NADPH oxidase 4 (NOX4) and p-p38 MAPK were detected by immunohistochemistry and Western blot assay. Results　Compared with the normal group, the blood glucose, Scr, BUN, MDA and the expressions of NOX4 and p-p38 MAPK were increased significantly in the model group, while the SOD activity decreased significantly (P＜0.05). Compared with the EECP 50 mg/kg group, the blood glucose, Scr, BUN, MDA, and expressions of NOX4 and p-p38 MAPK were significantly decreased in the EECP 100 mg/kg group, EECP 200 mg/kg group and the metformin group, and the SOD activity was significantly increased (P＜0.05). Compared with the EECP 100 mg/kg group and the EECP 200 mg/kg group, the blood glucose, Scr, BUN, MDA and expressions of NOX4 and p-p38 MAPK were significantly reduced in the metformin group, and SOD activity was significantly increased (P＜0.05). Conclusion　EECP can improve the renal injury of diabetic rats by reducing blood glucose and enhancing antioxidative ability, and the mechanism may be realized by inhibiting p38 MAPK/NOX4 signal pathway.

Key words: diabetic nephropathies, propolis, oxidative stress, p38 mitogen-activated protein kinases, NADPH oxidase