Aerobic exercises alleviate renal oxidative stress injury in a mouse model of diabetic nephropathy / 中国组织工程研究

ABSTRACT

BACKGROUND: Studies have confirmed that long-term regular aerobic exercise can effectively reduce blood glucose level and improve insulin resistance. It is an important measure for diabetic nephropathy, but the specific mechanism is unknown. OBJECTIVE: To investigate the effect of aerobic exercise on renal oxidative stress injury in mice with diabetic nephropathy, and explore its relationship with nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signal pathway. METHODS: Male C57/BL6 mice were randomly divided into normal control group, model group, and aerobic exercise group, 8 mice in each group. Except for the control group, mice in the other two groups were intraperitoneally injected with 40 mg/kg streptozotocin for 5 consecutive days to induce diabetes. After 4 weeks, the 24-hour urine protein content > 30 mg suggested a successful modeling of diabetic nephropathy. After 8 weeks of modeling, mice in the aerobic exercise group underwent treadmill aerobic exercise for 8 weeks, 1 hour daily, 5 days per week. After 8 weeks of treatment, systolic blood pressure of the tail artery, 24-hour urinary microalbumin excretion rate, blood glucose, blood lipid, serum creatinine, and blood urea nitrogen levels were measured. The content of malondialdehyde and the activity of total superoxide dismutase of renal tissue homogenate were determined. The glomerular mesangial extracelluar matrix deposition, the level of reactive oxygen and the expression levels of Nrf2 and HO-1 in renal tissue were detected. Ethic approval was obtained from the Experimental Animal Ethic Committee of Henan Academy of Chinese Medicine in China (approval No. HPHT2015019). RESULTS AND CONCLUSION: Compared with the control group, the 24-hour urinary microalbumin excretion rate, levels of blood glucose, serum creatinine, blood urea nitrogen, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol, and systolic blood pressure of the tail artery in the model group were significantly increased (P < 0.05), the glomerular mesangial extracelluar matrix was significantly accumulated (P < 0.05), and the levels of reactive oxygen species and malondialdehyde were significantly increased. Compared with the model group, the above-mentioned parameters were significantly decreased in the aerobic exercise group. Aerobic exercise significantly increased the activity of total superoxide dismutase, decreased the accumulation of glomerular mesangial extracelluar matrix, and up-regulated the expression of Nrf2 and HO-1 in the renal tissue. To conclude, aerobic exercise can alleviate renal oxidative stress injury in diabetic nephropathy mice, which may be related to the activation of Nrf2/HO-1 pathway.