Study Of The Protective Effect Of Ryanodine Receptor Antagonist Dantrolene On The Skeletal Muscle Ischemia Reperfusion Injury

OBJECTIVE A model of rat hind limb ischemia and reperfusion was established in this study.The study investigated the protective effect of the ryanodine receptor and intracellular calcium antagonist dantrolene on the skeletal muscle ischemia reperfusion injury.METHODS 24 male Sprague-Dawley rats were randomly divided into three groups(n=8/group):A(Sham)group that underwent anesthesia and exposure of the left femoral vein as other groups, B(Ischemia reperfusion)group that were subjected to 2 h of ischemia followed by 4 h of reperfusion and received only the amount of diluent(5% mannitol)at the time of reperfusion, C(Dantrolene)group that were subjected to 2 h of ischemia followed by 4 h of reperfusion and received dantrolene 2 mg/kg(dissolved in 5% mannitol)at the time of reperfusion. The parameters measured at 4 h of reperfusion included serum maleic dialdehyde ( MDA ) , tissue myeloperoxidase(MPO), and TNF-α, IL-10 in serum as well as skeletal muscle histology.RESULTS The levels of MDA, MPO, and TNF-αincreased significantly in the Ischemia reperfusion group, whereas the relevant expressions in the Dantrolene group decreased significantly(P<0.05)(MDA(nmol/ml,M±SD):A group 5.25±0.91,B group 9.41±1.72,C group 6.20±1.07;MPO(U/g,M±SD):A group 0.79±0.13,B group 2.54±0.31,C group 1.22±0.20;TNF-α(pg/ml,M±SD):A group 25.1±9.0,B group 631.5±80.8,C group 388.0±44.3 ) . Histological examination also demonstrated significant improvements between the same both groups. IL-10 reflected the protection observed above with a significant up-regulation of expression after dantrolene 2mg/kg(P<0.05)(IL-10(pg/ml,M±SD):A group 25.4±8.5,B group 54.2±13.3,C group 763.8±69.1).CONCLUSION In this study, we demonstrated that the ryanodine receptor and intracellular calcium antagonist dantrolene offered significant protection from the inflammatory injury of the rat skeletal muscle ischemia reperfusion. The probable mechanism was the down-regulation of the expression of TNF-αand the increment of the protective cytokine IL-10.