title: Effect of ischemic preconditioning on P-selectin expression in hepatocytes of rats with cirrhotic ischemia-reperfusion injury.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of ischemic preconditioning (IPC) on the ischemia/reperfusion (I/R) injury of liver cirrhosis in rats and the effect of IPC on P-selectin expression in hepatocytes.
  
  
  METHODS
  Forty male SD rats with liver cirrhosis were randomly divided into sham operation group (SO group), ischemia/reperfusion group (I/R group), ischemic preconditioning group (IPC group), L-Arginine preconditioning group (APC group), L-NAME preconditioning group (NPC group), eight rats in each group. Hepatocellular viability was assessed by hepatic adenine nucleotide level and energy charge (EC) determined by HPLC, ALT, AST and LDH in serum measured by auto- biochemical analyzer and bile output. The expression of P-selectin in the liver tissue was analyzed by immunohistochemical technique. Leukocyte count in ischemic hepatic lobe was calculated.
  
  
  RESULTS
  At 120 min after reperfusion, the level of ATP and EC in IPC and APC groups was higher than that in I/R group significantly. The increases in AST, ALT and LDH were prevented in IPC and APC groups. The livers produced more bile in IPC group than in I/R group during 120 min after reperfusion (0.101+/-0.027 versus 0.066+/-0.027 ml/g liver, P=0.002). There was a significant difference between APC and I/R groups, (P=0.001). The leukocyte count in liver tissues significantly increased in I/R group as compared with SO group (P<0.05). The increase in the leukocyte count was prevented in IPC group. Administration of L-arginine resulted in the same effects as in IPC group. However, inhibition of NO synthesis (NPC group) held back the beneficial effects of preconditioning. Significant promotion of P-selectin expression in hepatocytes in the I/R group was observed compared with the SO group (P<0.01). IPC or L-arginine attenuated P-selectin expression remarkably (P<0.01). However, inhibition of NO synthesis enhanced P-selectin expression (P<0.01). The degree of P-selectin expression was positively correlated with the leukocyte counts infiltrating in liver (r=0.602, P=0.000).
  
  
  CONCLUSIONS
  IPC can attenuate the damage induced by I/R in cirrhotic liver and increase the ischemic tolerance of the rats with liver cirrhosis. IPC can abolish I/R induced leukocyte adhesion and infiltration by preventing post-ischemic P-selectin expression in the rats with liver cirrhosis via a NO-initiated pathway.
authors.affiliation: Department of Hepatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China. chengxd516@sohu.com
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Cheng
authors.forename: Xian-Chuan
authors.initials: XC
authors.lastname: Jiang
authors.forename: Yin-Bing
authors.initials: YB
authors.lastname: Liu
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Peng
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Shu-You
authors.initials: SY
authors.lastname: Peng
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D004734:Energy Metabolism; D022781:Hepatocytes / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D008103:Liver Cirrhosis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase