Abstract:Objective：To determine the delayed protective effect of diazoxide(DE), as an ischemic preconditioning (IPC) simulator, on inhibition of ischemia/reperfusion induced hepatocyte apoptosis in rats.
Methods ：Four groups of SD rats (n=8 each) were pretreated with: (1) 5-min period of liver ischemia (IPC group); (2) DE 5mg/kg iv (DE group), (3) DE plus 5-hydroxydecanoate (DE+5-HD group), and (4) with saline(control or C group). Twenty-four hours later, the pretreated rats were subjected to 60-min sustained liver ischemia followed by 180-min reperfusion. All rats were only subjected to 70% liver ischemia. An additional fifth (S)group of rats (sham group) was set up, in which only anesthesia and laparotomy were performed twice. Finally, liver samples were obtained to determine apoptotic cells by TUNEL, and the expressions of Bcl-2 protein by immunohistochemical technique, and pathology.
Results：Apoptosis index were higher in C group than those in S group (P<0.01). There were also severe morphologic damages in C group. The levels of expression of Bcl-2 protein were increased (P<0.01) and apoptosis index were decreased (P<0.05) in IPC group and DE group compared with C group. DE+5-HD group had the opposite changes, contrasted to DE group (P<0.05,P<0.01).
Conclusions：DE can mimic the delayed protective effects of IPC, and induce delayed protection against hepatocyte apoptosis, possibly due to increased expression of the Bcl-2 protein.