Objective: To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
Methods: Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min- reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
Results: At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
Conclusion: RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.
目的：探讨肢体远程缺血预处理(remote ischemic preconditioning，RIPC)对肝脏缺血/再灌注损伤的影响及其机制。方法：对大鼠进行局部的肝组织缺血再灌注(缺血60 min后再灌注24 h)，缺血前30 min通过3个循环的双侧股动脉闭塞10 min和再灌注10 min来实现RIPC。在RIPC之前，用PPAR-γ抑制剂T0070907处理部分大鼠。结果：在再灌注结束时，局部缺血后肝损伤显著增加Suzike的损伤评分和AST及ALT释放，并伴随有氧化应激和炎症反应增加。RIPC能够改善肝脏缺血/再灌注后的肝功能，减少肝组织病理损伤，与PPAR-γ活化和自噬体增多相关。PPAR-γ抑制剂T0070907显著减少自噬体形成，抑制RIPC对肝脏缺血/再灌注损伤的保护作用。结论：肢体远程缺血预处理是通过活化的PPAR-γ激活肝脏自噬，从而对肝脏起保护作用。.