Astragaloside IV protects against ischemia reperfusion in a murine model of orthotopic liver transplantation.

ABSTRACT

AIM: The aim of this study was to determine whether Astragaloside IV (AST-IV) inhibited the transcriptional activity of nuclear factor-κB (NF-κB), attenuating liver transplant ischemia-reperfusion injury (IRI). METHODS: Sprague Dawley (SD) rats were randomly divided into 2 groups donors given AST-IV (1.5 mL; 100 µg/mL, intravenous [IV]) 1 hour before surgery (n = 32), versus controls treated with 1.5 mL physiological saline (n = 32). Orthotropic liver transplantation was performed according to the Kamada technique. Eight animals in each group were followed for seven days after surgery to assess survival. The remaining hosts in each group were divided into 3 subgroups (n = 8) to be examined at 3, 6, and 24 hours after portal vein reperfusion. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, and NF-κB transcriptional activity and performed a morphological study of liver tissues, NF-κB, and glucocorticoid receptor (GR) expression in Kupffer cells (KCs). RESULTS: Pretreatment with AST-IV significantly improved survival rates and liver function, attenuating liver parenchymal cell damage by down-regulating TNF-α levels and NF-κB expressions, inhibiting NF-κB transcriptional activity, up-regulating GR expression. CONCLUSION: AST-IV attenuated hepatic IRI by inhibiting NF-κB transcriptional activity. The mechanism may relate to up-regulation of GR expression.