Effect Of Phosphocreatine On Hepatic Ischemia Reperfusion Injury In Rats

Objective PCr is a very important energy substrate, which can go through theblood-brain barrier, even through the cell membrane, to supply energy to cells directly.There are many studies indicate that PCr preconditioning can attenenuated cellapoptosis and the morphological damage during cerebral ischemia-reperfusion in rats.In ischemia reperfusion injury brain, the apoptotic neurons extensively exist. Thepurpose of this study was to investigate the effects of different doses of Pcr on partialischemia/reperfusion injury in rats and its mechanism.Methods Thirty male SD rats weighing250-300g were randomly divided into5groups(n=6each)：group I sham operation(S)；groupⅡ I/R；group Ш、IV、V are PCrtreatment groups, PCr in dose of50、150and450mg/kg was administeredintravenously30min before the occlusion of the left lateral and median lobes of theliver. Each group observed indicators; Liver Myeloperoxidase (MPO)、serum alanineaminotransferase (ALT)、aspartate aminotransferase (AST)、serum interleukin-1β(IL-1β) and tumor necrosis factor alpha (TNF-α)、 the expression of ICAM-1byimmunohistochemistry、apoptosis(by TUNEL)in hepatic cells. the apoptotic indexwas calculate.Results Compared with Sham group, I/R group at ischemic90min reperfusion after4h,the ALT、AST、TNF-α、IL-1β、MPO activity was significantly increased in serumand liver tissue homogenate（P<0.05）.Compared with I/R group, pretreatment of ratswith50、150and450mg/kg Pcr were markedly decreased ALT、AST、TNF-α、IL-1β、MPO activity in serum and liver tissue homogenate（P<0.05）.The damage to livercells induced by I/R was significantly less severe in group PM、 PH than group I/R. The apoptotic index was significantly lower in group PM、 PH than group I/R（P<0.05）.Compared with Sham group, the expression of ICAM-1in I/R group wassignificantly increased in liver tissue homogenate（P<0.05）. Compared with I/R group,pretreatment of rats with50、150and450mg/kg Pcr were markedly decreased theexpression of ICAM-1in liver tissue homogenate.Conclusion The phosphocreatine pretreatment can attenuate the hepatic I/R injurythrough inhibiting inflammatory response to decrease neutrophil adhesion to vascularendothelial cells in rats and it is related to the dose.