Ryanodine receptor antagonism alleviates skeletal muscle ischemia reperfusion injury by modulating TNF-α and IL-10

BACKGROUND: Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury. MATERIALS AND METHODS: SD rats were randomly divided into three groups: sham group which underwent anaesthesia and exposure of femoral vein, reperfusion group that received 2 h ischemia and the amount of diluent via femoral vein before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion. The parameters measured at the end of reperfusion included serum maleic dialdehyde (MDA), tissue myeloperoxidase (MPO) and muscle histology, as well as serum TNF-alpha and IL-10. RESULTS: Levels of MDA, MPO and TNF-alpha increased in the reperfusion group, whereas the relevant expressions in the dantrolene group decreased significantly. Histological examination demonstrated significant improvements between the same both groups. IL-10 reflected the protection observed above with a significant up-regulation of expression after dantrolene administration. CONCLUSION: Ryanodine receptor antagonist dantrolene exerted a significant protective effect against the inflammatory injury of skeletal muscle ischemia reperfusion. The underlying molecular mechanism is probably related to the suppression of TNF-alpha levels and the increment of IL-10 expression.