Enalapril inhibits tubulointerstitial inflammation and NLRP3 inflammasome expression in BSA-overload nephropathy of rats.

Abstract

Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats. Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg(-1)·d(-1), ip), or BSA plus enalapril (0.5 g·kg(-1)·d(-1), po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot. BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68(+) cells (macrophages) and CD3(+) cells (T lymphocytes), particularly of CD20(+) cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril. Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.