PROTECTION OF ISCHEMIA REPERFUSION INJURY IN MURINE LIVER BY GENE SILENCING OF COMPLEMENT 3

It has been documented that ischemia reperfusion injury (IRI) in the liver is associated with complement pathway activation. Thus, blocking complement 3 (C3) genes using a small hairpin RNA (shRNA) can potentially prevent liver IRI. Gene silencing of C3 in vivo was achieved via the administration of shRNA prior to IRI. Liver IRI was evaluated using histopathology, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Neutrophil accumulation was determined by myeloperoxidase assay. Oxidative stress was assessed by malondialdehyde and reactive oxygen species levels. In comparison with control mice treated with scrambled shRNA, the serum levels of ALT and AST were significantly reduced in mice treated with C3 shRNA. Additionally, neutrophil accumulation and lipid peroxidase-mediated tissue injury were decreased after shRNA treatment. Tissue histopathology showed an overall amelioration of injury in shRNA-treated mice. Therefore, the silencing of the C3 gene proved to be a potential therapy for preventing hepatic IRI