The Study Of Protective Mechanism Of Ischemic Preconditioning For The Liver Injury Of Ischemia Reperfusion In Rats

In the hepatic surgery,temporary occulusion of the hepatic inflow,or the donor liver for liver transplantation inevitablly results in a serious liver injury of ischemia/reperfusion(IR).Although the pathophysiologic mechanisms of IR injury to the liver are not completely understood,the more and more studies show that apoptosis is one of the mechanisms of IR injury.Cystein-dependent aspartate-specific proteinases (Caspases) are proteases related to human interleukin-1 ?convert enzyme(ICE) and the nematode cell-death gene CED3.Caspases are the central effectors in apoptosis signaling pathways. Apoptosis has been thought to be one of the main factors in the liver injury of IR.It is very important to improve the liver against the injury of IR.Caspase-3 is one of the Caspase family members and is a key protease to cleave substrate in the down pathway of apoptosis.lt will induce cell apoptosis when Caspase-3 is activiated. Ischemic preconditioning(IP) protects various tissues against subsequent IR injury,but its protective mechanism is still not clear.Based on above informations,we develope the hyothesis that protective effect of IP to liver IR injury may be through the downregulation of caspase to inhibit apoptosis .The treatment of Caspase inhibitors may inhibit caspase activity results in decreasing apoptosis of hepatocytes and then protect the liver against IR injury,which is of great significance in clinical work. Comparing the protective effect of Caspase inhibitors treatment with IPIVon the liver IR injury is also an aim of this study. This study have two sections.Section 1The changes of Caspase-3 activity of ischemia reperfusion injury in rats and the protective mechanism of ischemic preconditioningObjective To investigate Caspase-3 activity changs in the ischemia reperfusion (IR) injury in rats and the protective mechanism of ischemic preconditioning on IR injuring. Methods 30 SD rats were randomly divided to three groups:(l)ischemia reperfusion(IR) group; (2) Ischemic preconditioning(IP) group; (3)Sham-operation(S)group. The serum aspartate transaminase (AST^ alanine transaminase(ALT), liver Caspase-3 activity, and hepatocytes apoptosis index(AI) were examined in the three groups at 3 hours reperfusion after 120min ischemia. Results (l)The levels of serum AST > ALTJiver Caspase-3 activity and hepatocytes apoptosis were significantly higher in group IP and IR than those in group S (P<0.01) ,and that in group IR was significantly increased compared with that in group IP (P<0.01) .Electron microscope displayed the damage of organelles was mider in group IP than in that group IR and no change of organelles in group S. Conclusions IR injury may activate the apoptosis of hepatocytes by increasing Caspase-3 actinity,and lead to aggravate the injury of liver.IP can reduce IR injury ofliver, and its possible mechanism is that IP may downregulate Caspase-3 activity to inhibite apoptotic hepatocytes.