Chronic intermittent hypobaric hypoxia ameliorates diabetic nephropathy through enhancing HIF1 signaling in rats.

Objective: Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had anti-diabetes effect. The present study was to explore the renal protective effect of CIHH in diabetic rats.

Methods: Sprague-Dawley rats were randomly divided into three groups: diabetes mellitus group (DM, induced by high-fat diet combined with low-dose streptozotocin), diabetes plus CIHH treatment group (DM+CIHH, simulated 5000-m altitude, 6h per day for 28days, after diabetes model confirmed) and control group (CON). Systolic arterial blood pressure (SAP), blood biochemicals, urinary albumin, and histopathology of kidney were determined. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, protein levels of hypoxia induced factors (HIFs) and transforming growth factor β1 (TGF-β1) in kidney were assayed.

Results: The increased SAP, urinary albumin, hyperplasia of glomerular, fibrosis in mesangial and glomerular, and abnormal lipid metabolism in diabetic rats were ameliorated by CIHH treatment. And decreased superoxide dismutase (SOD) activity and increased malondialdehyde (MDA) level in diabetic kidney were reversed in CIHH-treated DM rats. In addition up-regulated TGF-β1 and down-regulated HIF1α in diabetic kidney returned back to normal level in CIHH-treated DM rats.

Conclusions: These data demonstrated for the first time that CIHH had protective effects against the early stage damage of diabetic nephropathy through activating HIF1 signaling, improving anti-oxidation and inhibiting TGF-β1 signaling in diabetic rats.