Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement.

METHOD

Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-B, SIRT1, and PGC-1 in the skeletal muscles were detected by western blot. Blood TNF- levels, gastrocnemius muscle contractile force, and ATP concentration were examined.

RESULTS

Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF- levels, and inhibited the expression levels of TLR4/NF-B in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1 levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels.

CONCLUSION

Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-B-dependent inflammatory response and protects SIRT1/PGC-1-dependent mitochondrial function.