Astragaloside IV Inhibited Podocyte Pyroptosis in Diabetic Kidney Disease by Regulating SIRT6/HIF-1α Axis.

Abstract

To investigate the effect of astragaloside IV (AS) on podocytes pyroptosis in diabetic kidney disease (DKD). Forty male Sprague-Dawley rats were randomly divided into normal group (n = 10) and model group (n = 30). Rats in model group were intraperitoneally injected streptozotocin (60 mg/kg) for 3 days to induce DKD. Then rats were divided into DKD group, AS group, and UBCS group. The AS group was given 40 mg/kg/d of AS by gavage, and UBCS group was given 50 mg/kg/d of UBCS039 by gavage, and normal group and DKD group were given the same amount saline for 8 weeks, once a day. Hematoxylin-eosin and masson staining were used to observe pathology of kidney. Rat podocytes were divided into normal group, mannitol hypertonic group, high-glucose group, UBCS group, OSS group, and AS group. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to analyze pyroptosis-related markers and reactive oxygen species (ROS) levels. Results showed that AS inhibited ROS and alleviated podocytes pyroptosis in rats by increasing expression of sirtuin 6 (SIRT6) and decreasing expression of hypoxia inducible factor 1 subunit alpha (HIF-1α). UBCS039 and AS enhanced SIRT6 level, decreased HIF-1α level, and finally improved pyroptosis of podocytes in vitro, whereas OSS-128167 showed the opposite effect for podocytes pyroptosis. AS improved podocytes pyroptosis in DKD by regulating SIRT6/HIF-1α pathway, thereby alleviating injury of DKD.