Effects Of Dexmedetomidine On Hepatic Ischemia Reperfusion Injury In Rats With Cholestasis And Liver Fibrosis

Objective: To investigate the effects of dexmedetomidine(Dex) on hepatic ischemia reperfusion injury(IRI) in rats with cholestasis and liver fibrosis.Methods: Model of rats with cholestasis and liver fibrosis is established by bile duct ligation(BDL). Thirty-two male modeled SD rats were randomized into four groups(n=8): ①Sham operated group(group S): rats underwent laparotomy, 5mL/kg normal saline(NS) was injected intraperitoneally, the hepatic pedicle was not occluded, after 60 min, the abdomen was closed, 4h later, the rats were laparotomized again, and were sacrificed after blood sample and liver tissues were obtained. ②Group IRI: rats underwent laparotomy and 5mL/kg NS injection, 30 min later, the hepatic pedicle was occluded for hepatic ischemia, after 30 min, the occlusion was relieved, the procedures later were done as described in Group S. ③ 10μg/kg Dex and IRI group(Group D10): rats was laparotomized and Dex 5mL/kg(2μg/mL) was injected intraperitoneally, 30 min later, the hepatic pedicle was occluded, then the procedures were done as described in Group IRI. ④100μg/kg Dex and IRI group(Group D100): rats were laparotomized and Dex 5mL/kg(20μg/mL) was injected intraperitoneally, 30 min later, the hepatic pedicle was occluded, then the procedures were done as described in Group IRI. 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) level. Liver tissues were obtained for analysis of superoxide dismutase(SOD) and malondialdehyde(MDA) activity, and were observed after hemotoxylin-eosin(HE) or Masson staining for histopathological assessment.Results: Serum TBIL and DBIL level① s: there were no significant differences between four groups(P>0.05). ②AST and ALT levels in serum: AST in Group IRI, D10 and D100 were significantly higher than in Group S(P<0.05), AST in Group D10 and D100 were both lower than in Group IRI(P<0.05), AST in Group D100 is significantly lower than in Group D10(P<0.05). ALT in Group IRI was significantly higher than in Group S, ALT in Group D100 was significantly lower than in Group IRI. ③SOD activities and MDA concentrations in liver tissues: SOD in Group IRI, D10 and D100 were significantly lower than in Group S(P<0.05),SOD in D10 and D100 were both significantly higher than in Group IRI(P<0.05). MDA in Group IRI, D10 and D100 were significantly higher than in Group S(P<0.05),MDA in D10 and D100 were both significantly lower than in Group IRI(P<0.05). ④ TNF-α concentrations in serum: TNF-α in Group IRI, D10 and D100 were significantly higher than in Group S(P<0.05), TNF-α in D10 and D100 were both significantly lower than in Group IRI(P < 0.05). ⑤ Histopathological changes: 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.Conclusion: 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 concentration.