Abstract

To investigate the role of HO-1 in ischemic preconditioning and pharmacological preconditioning by ulinastatin in attenuating remote lung injury in rat model of lower limb ischemia reperfusion. Sixty four male SD rats were randomly divided into four groups: Sham operation group, ischemia and reperfusion group, ischemia preconditioning group (IPR), ulinastatin preconditioning group (UTI). The animals were deeply anesthetized and the lung tissue was removed at the end of the experiment. Lung W/D ratio were measured and the expression of HO-1 was determined by Immunohistochemical staining and western blotting. HO-1 was induced and expressed persistently in 2 and 4 h after ischemic preconditioning and ulinastatin preconditioning (P<0.01), and the expression in 4 h was higher than 2 h in preconditioning groups (P<0.05). The preconditioning also led to diminished lung edema (W/D ratio) (P<0.05 vs I/R), with no differences when compared to the sham group. The induction of HO-1 by ischemic preconditioning and ulinastatin preconditioning played a protective role against remote lung injury in the model of limb injury/reperfusion.   Key words: Heme oxygenase-1, preconditioning, ulinastatin, ischemia/reperfusion.

Highlights

  • Lower limb ischemia followed with reperfusion is an important and common clinical event

  • Li-hua et al 665 study, we examined that whether the protection of Ischemic preconditioning (IPC) and pharmacological preconditioning correlated with upregulation of the expression of HO-1

  • Afer 30 min the animals were subjected to 2 h of ischemia followed by 2 h (n=8) or 4 h (n=8) of reperfusion. (III) The ischemia proconditioning group (IPR): the bilateral femoral artery were exposed to three cycles of ischemic proconditioning (5 min of ischemia followed by 5 min of reperfusion) sebsequent 2 h of ischemia followed by 2 h of reperfusion (n=8) or 4 h of reperfusion (n=8). (IV) Urinary trypsin inhibitor proconditioning group (UTI) three minutes before the ischemia urinary was injected through the left jugular (50000 U/kg, dilutied in 1 ml NS) under 2 h ischemia followed by 2 and 4 h reperfusion

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Summary

Introduction

Lower limb ischemia followed with reperfusion is an important and common clinical event. Both clinical observation and animal experiment indicate that the reperfusion can save the limbs but result in multisystem organ dysfunction, and even death in extreme cases. The infiltration and activation of neutrophils and oxygen free radicals generated in the reperfused extremity are considered to be responsible for this process. In response to oxidative stress, cell often synthesize specific antioxidant proteins, such as superoxide dismutase, catalase and glutathione peroxidase. One protein that was found to be activated by oxidative stress is the heme degrading enzyme, hemeoxygenase (HO), Li-hua et al 665 study, we examined that whether the protection of IPC and pharmacological preconditioning correlated with upregulation of the expression of HO-1

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