Leaky gut potentially leads to bacterial/endotoxin translocation in a rat model of non-ischemic acute kidney injury

Abstract Background: Emerging evidence indicates that there is a causal relationship between acute kidney injury (AKI) and gut barrier disruption. The aim of our study was to determine whether the translocation of gut-derived bacteria/endotoxin develops in non-ischemic AKI, and, if so, what is the mechanism behind it? Methods: SPF male Sprague-Dawley rats were randomly subjected to bilateral nephrectomy (BNx) or sham-operation and observed for 24 hours. Gut permeability was evaluated in vivo and in vitro. Serum endotoxin and bacterial loads in liver and mesenteric lymph nodes (MLN) were measured. The expression of the key tight junctions (TJs) in ileum, including zonula occluden-1(ZO-1), occludin and claudin-1 were evaluated by Western blot and immunohistochemical staining. The structure of TJs was observed using transmission electron microscopy. Apoptotic changes of ileal mucosa were evaluated by TUNEL staining and ELISA. Results: Non-ischemic AKI rats (rats subjected to BNx) demonstrated marked blunting and shortening of the gut villi. The gut mucosal permeability was increased in non-ischemic AKI rats, evidenced by the elevated serum levels of D-lactate and the increased amount of FITC-Dextran which passed through the ileum wall. Serum endotoxin was significantly elevated in non-ischemic AKI rats. Non-ischemic AKI rats had relatively higher bacterial loads in liver and MLN than sham-operated rats. For non-ischemic AKI rats, apoptosis of ileal mucosa was significantly accelerated. Neither the protein expression and the distribution pattern, nor the structure of the TJs was altered in non-ischemic AKI rats. Conclusion: Non-ischemic AKI results in profound gut barrier disruption and thus favors the subsequent episode of bacterial/endotoxin translocation. In this non-ischemic AKI model, the translocation of bacterial/endotoxin was not most likely due to a TJs mediated paracellular pathway.