PS-B08-4: CHRONIC INTERMITTENT HYPOXIA INDUCES RENAL FIBROSIS BY MR ACTIVATION

Purpose: Obstructive sleep apnea is mainly characterized by chronic intermittent hypoxia (CIH), which is associated with chronic kidney disease. Macrophage is known to play an important role in renal fibrosis. However, little is known of the potential role of macrophage-to-myofibroblast transition (MMT) in hypoxic conditions. The aim of this study was to understand how infiltrating macrophages may contribute to renal fibrosis in hypoxic conditions. Methods: In this study, 30 adult male sprague dawley (SD) rats were randomly divided into normoxic control(NC), chronic intermittent hypoxia(CIH), and eplerenone(EPL) groups-each containing ten rats. The CIH and EPL groups were exposed to hypoxia in a commercial hypoxic chamber for 5 weeks. Rats in the EPL group were administered EPL orally via diet for 5 weeks. All rats were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, western blot, immunohistochemistry. The RAW264.7 macrophages were subjected to 24 hours of hypoxia and 12 hours of reoxygenation. Cells were collected for immunofluorescence staining. Results: In addition to blood pressure, renal aldosterone level was also increased in CIH rats. Massons trichrome and Sirius red staining showed significantly higher collagen deposition and fibrosis in CIH rats. A markedly increased co-expression of α-SMA and CD68 in vitro and in vivo after CIH exposure. MR nuclear translocation was seen in hypoxic macrophages. Western blot showed that the expression of SGK-1 and p-SGK-1 was upregulated. These effects were reversed by MR blocker (EPL). Conclusions: CIH-induced macrophage infiltration, an important source of myofibroblasts, might participate in the development of renal interstitial fibrosis. These effects were reversed by EPL. Therefore, we speculate MR activation may be related to CIH-induced renal fibrosis.