Background: Remote ischemic preconditioning (RIPC) has been shown to reduce ischemic injury in an ex vivo mice hepatic ischemia reperfusion (IR) model and diazoxide is known to attenuate ischemic injuries in several organ models via the ATP-activated potassium channel [K(ATP)] pathway. However, the combined effect of those two interventions has not been tested in mice hepatic ischemia reperfusion model. This study aimed to investigate the effect in vivo using a mice hepatic ischemia reperfusion model.
Methods: Forty c57BL6 mice were randomly divided into the following 5 groups: i) sham-operated control; ii) IR; iii) IR+RIPC; iv) IR+RIPC+diazoxide; v) IR+RIPC+glyburide. The histological changes including the hepatic ischemia injury were assessed by H&E staining and the levels of liver aminotransferase enzymes and inflammatory cytokines (IL-6, IL-8 and TNF-alpha) were measured. 
Results: Both diazoxide and RIPC significantly reduced the hepatic ischemic injury, liver enzymes and inflammatory cytokine secretion compared with ischemia reperfusion group. Furthermore, the combination of diazoxide and RIPC had a synergic hepatic ischemia limiting and anti-inflammatory effects. On the other hand, combination of glyburide and RIPC increased acute liver injury compared with RIPC alone, thereby attenuating the hepatic ischemia limiting and anti-inflammatory effect of RIPC.  
Conclusions: The findings of this study suggested that the combination of diazoxide and RIPC had a potentially hepatic ischemia preventing effect via the K(ATP) pathway.


02 / Remote Ischemic Preconditioning combined with Diazoxide Attenuates from Hepatic Ischemia Reperfusion Injury Induced by Ischemia and Reperfusion