PKC beta inhibitor prevents renal ischaemia‒reperfusion injury by affecting macrophage infiltration and polarization

Abstract

Abstract Background Acute kidney injury (AKI) secondary to renal ischemia reperfusion injury (RIRI) continues to be a significant perioperative problem and there is no effective treatment. We previously reported that proteinkinase (PKC) β inhibitor could attenuate RIRI after kidney transplantation in rats. However, the mechanism by which PKC β inhibitor protects against RIRI remains unclear. Methods RIRI [Ed1] model rats were subjected to right nephrectomy and clipping of the left renal pedicle for 60 minutes. The PKC β inhibitor was orally administered the day before surgery. The rats were sacrificed 24 hours after the operation, and blood and kidney samples were collected. Renal function, histomorphology, renal tubular injury marker KIM-1，renal papillary injury indicator RPA-1，macrophage subtype markers and inflammatory cytokines were analysed. Results The results showed that the PKCβ inhibitor had a protective effect against RIRI, as indicated by the attenuation of renal dysfunction and a reduction in renal injury. In addition, the PKC β inhibitor significantly reduced the expression of the M1 macrophage marker CD197 and increased the expression of the M2 macrophage marker CD163[Ed2] . The expression of the proinflammatory cytokines iNOS and IL-12 was downregulated, while the expression of the anti-inflammatory cytokines Arg-1 and Dectin-1 was upregulated by the PKCβ inhibitor. Conclusions The PKCβ inhibitor can alleviate RIRI in rats to some extent, which may be related to improve tubular damage in ischemic renal tissue and promoting the polarization of macrophages to the M2 phenotype.