Abstract
Back ground: Liver complicated with cholestasis and fibrosis is vulnerable to ischemia reperfusion injury (IRI). Objectives: To investigate the effects of dexmedetomidine on hepatic ischemia reperfusion injury in rats with cholestasis and liver fibrosis. Material and Methods: Model of rats with cholestasis and liver fibrosis is established by bile duct ligation (BDL) for 18 days. Thirty-two male modeled SD rats were randomized into four groups (n=8): Group S: rats underwent laparotomy but the hepatic pedicle was not occluded. Group IRI: the hepatic pedicle was occluded for 30min. Group D10: dexmedetomidine 10μg/kg was injected intraperitoneally before hepatic ischemia. Group D100: dexmedetomidine 100μg/kg was injected intraperitoneally before hepatic ischemia. Blood samples were obtained for analysis of total billirubin (TBIL), direct billirubin (DBIL), aspertate transaminase (AST), alanine transaminase (ALT), and tumor necrosis factor-α (TNF-α). Liver tissues were obtained for analysis of superoxide dismutase (SOD) and malondialdehyde (MDA), and were observed after hemotoxylin-eosin (HE) or Masson staining for histopathological assessment. Results: TBIL and DBIL values were not significantly different between four groups (P > 0.05). AST, MDA and TNF-α values in group IRI, D10 and D100 were significantly higher than in group S, while SOD value were lower (P < 0.05), AST, MDA and TNF-α values in group D10 and D100 were significantly lower than in group IRI, while SOD values were higher (P < 0.05). The degrees of bile duct proliferation and fibrosis in liver tissues in four groups were similar. In group IRI, there were severe inflammatory cells infiltration, hepatocellular swelling and even local necrosis in liver tissue, but injuries in group D10 and D100 was moderate. Conclusions: Dexmedetomidine may attenuate hepatic IRI in rats with cholestasis and liver fibrosis, possibly by up-regulation of SOD activity and down-regulation of TNF-α expression.
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