Potential Protective Effect of Nuclear Factor-kappa B Decoy Oligodeoxynucleotides on Endotoxin-induced Liver Injury

作者:Li, J. D.*; Peng, Y.; Li, Q.; Xiao, J. W.; Gong, J. P.; Liu, Z. J.
来源:Transplantation Proceedings, 2011, 43(10): 3613-3617.
DOI:10.1016/j.transproceed.2011.10.046

摘要

Purpose. We sought to study the protective effects of nuclear factor-kappa B decoy oligodeoxynucleotides (ODNs) on endotoxin-induced liver injury in a rat model. Methods. Sixty Sprague-Dawley rats were randomly divided into a control (n = 20), a lipopolysaccharide (LPS) (n = 20), and an NF-kappa B decoy ODN group (n = 20). Liver and blood serum samples were collected at 24 hours after the operation. NF-kappa B binding activity was detected by an electrophoretic mobility shift assay, liver histopathology, by light microscopy; and cell apoptosis, by a terminal-deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. The serum of liver enzyme (aspartate transaminase [AST]) levels were measured using an automated biochemical analyzer and tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 by enzyme-linked immunosorbent assays. Results. NF-kappa B was dramatically activated after endotoxin-induced liver injury. Many hepatocytes underwent degeneration and necrosis in the LPS group. The expressions of AST, TNF-alpha, and IL-6 were significantly increased compared with the control group (P = .0005), However, NF-kappa B decoy ODNs altered these undesirable changes. On the other hand, IL-6 expression was not significantly decreased by the NF-kappa B decoy versus the LPS group (P = .0745). Conclusions. NF-kappa B decoy strategy inhibited the binding activity of NF-kappa B, thus suppressing production of downstream cytokines which play crucial roles in protection from endotoxin-induced injury.

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