Inhibition of PARP overactivation protects acute kidney injury of septic shock

Y.-M. Wang, R.-L. Han, S.-G. Song, X.-P. Yuan, X.-S. Ren

ICU, Tianjin TEDA Hospital, Tianjin, China. trxsheng@163.com

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• Nephrology

OBJECTIVE: To evaluate pathological lesions in New Zealand white rabbits with acute kidney injury (AKI) of septic shock and to explore the potential role of poly (ADP-ribose) polymerase (PARP) in regulating AKI development.

MATERIALS AND METHODS: Endotoxic shock model in New Zealand white rabbits was first constructed. CVP (central venous pressure) was maintained at the baseline level by the saline administration. Rabbits were randomly assigned into sham group, LPS group, and LPS+3-AB group, respectively. Blood samples and kidney samples of rabbits were collected 4 h after LPS administration. Pathological kidney lesions were observed by HE (hematoxylin-eosin) staining and immunohistochemistry. Serum levels of renal damage markers (Scr, Cys-C, KIM-1, and NGAL) were detected by an automatic biochemical analyzer, immunoturbidimetry, and ELISA (enzyme-linked immunosorbent assay), respectively. Kidney energy metabolism changes (ATP, ADP, PCr, and NAD) were detected by HPLC (high performance liquid chromatography analysis). Western blot was conducted to detect protein expressions of NF-κB (nuclear factor-kappa B), TNF-α (tumor necrosis factor-α), ICAM-1 (intercellular cell adhesion molecule-1) and P-selectin in kidney tissues.

RESULTS: Significant pathological lesions in kidney tissues and higher pathological grade were seen in the LPS group. Multiple PARP-positive nuclei were found in renal tubular cells at the junction of renal cortex and renal cortex in the LPS group. Serum levels of Scr, KIM-1, NGAL, and Cys-C were remarkably higher in the LPS group than those of sham group. HPLC results showed decreased levels of ATP, ADP, PCr, and NAD in kidney cortex of LPS group compared with those of sham group. Western blot results suggested that protein expressions of NF-κB, TNF-α, ICAM-1, and P-selectin were remarkably upregulated in kidney tissues of LPS group. 3-AB pretreatment, the PARP inhibitor, remarkably alleviated pathological lesions and inflammation induced by AKI.

CONCLUSIONS: Inhibition of PARP overactivation alleviated pathological kidney lesions, improved kidney energy metabolism and inhibited inflammatory response resulted from AKI.

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