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Role of the activation of intedeukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury
Author(s): 
Pages: 863-567
Year: Issue:  11
Journal: Chinese Journal of Surgery

Keyword:  Reperfusion injuryEpithelial cellsRegeneration;
Abstract: Objective To investigate the role of IL-6/STAT3 pathway in the proliferation of cholangiocyte induced by cold ischemia and reperfusion injury. Methods Rats were randomized into CP 1 h and CP 12 h groups (supplied livers were preserved for 1 or 12 h) ,anti-IL-6R (rats in CP 12 h group were administrated with anti-rat soluble IL-6 receptor antibody), and control group. At 1,3,7,14 d postoperative, IL-6 concentration in liver homogenate and cholangiocyte proliferation were detected by enzyme linked immunosorbent assay and histocbemistry respectively. Expressions of IL-6 mRNA,phophorylated-STAT3 and cyclin D1 protein in cholangincytes were determined by real-time PCR or Western blot analysis. Serum concentrations of ALP and GGT and histology analysis were also pedormed. Results Minimal expressions of IL-6,p-STAT3 and cyclin D1 were detected in CP 1 h group, with a slight cholangiocytes proliferation. Cholangiocytes responded to extended cold preservation with severe bile duct injures and marked increase in IL-6 secretion, p-STAT3 and cyclinDl protein expression, followed by compensatory cholangiocytes regeneration. Parallel to this observation, biochemical index and morphology indicated that bile duct injury was recovery at 14 d postoperative. However, anti-sIL-6R inhibited cholangiocytes proliferation and reduced the expressions of IL-6, STAT3 and cyclin D, with the cellular injury and increase of serum ALP or GGT. Conclusions IL-6/STAT3 pathway might participate to initiate cholangiecytes regeneration after cold ischemia and preservation injury,which might benefit biliary recovery after fiver transplantation.
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