Abstract: Ｏｂｊｅｃｔｉｖｅ：To investigate effect and underlying mechanisms of a pyroptosis inhibitor, Bay117082, in treatment of membranous nephropathy (MN).
Ｍｅｔｈｏｄｏｌｏｇｙ：Bay117082 was administered to a C3a／C5ainduced podocyte injury model in vitro. Cell injury was evaluated according to propidium iodide (PI) staining and lactate dehydrogenase (LDH) release. Alterations in pyroptosis signaling pathways were observed through immunofluorescence, Westernblot and ELISA. Passive Heymann nephritis (PHN) rat model was established and treated with Bay117082. Renal and podocyte injuries were evaluated through 24h urine protein (24hUPro), serum albumin (ALB), renal histopathology, immunohistochemical staining of Desmin／WT1. Changes in pyroptosis signaling pathways were observed through immunofluorescence, immunohistochemistry, RTqPCR, Westernblot and ELISA.
Ｒｅｓｕｌｔｓ：Bay117082 ameliorated C3a／C5ainduced podocyte injury by inhibiting pyroptosis, as demonstrated by decreased percentage of PIpositive cells and LDH release along with downregulation of NFκBNLRP3ASCCaspase1IL18／GSDMD pyroptosis signaling pathway. Bay117082 alleviated renal and podocyte injuries in PHN rats by inhibiting pyroptosis, as reflected by improvement of renal injury, including decreased 24hUPro and Desmin expression in podocyte, increased ALB and WT1 expression in podocyte nuclei, and significantly alleviated podocyte foot process fusion under transmission electron microscopy. The NFκBNLRP3ASCCaspase1IL1β／IL18／GSDMD pyroptosis signaling pathway was also downregulated in the glomeruli.
Ｃｏｎｃｌｕｓｉｏｎ：Bay117082 alleviated renal lesions in MN by inhibiting complementinduced podocyte pyroptosis.