Anti‐inflammatory effect of PEGylated dexamethasone liposome for tourniquet‐induced acute ischemia‐reperfusion injury in mouse skeletal muscle (1102.5)

Abstract

Ischemia‐reperfusion (IR) triggers a cascade of cellular and systemic inflammation and leads to cellular apoptosis and tissue necrosis in the skeletal muscle. In present study we investigated if anti‐inflammation improves skeletal muscle function. Hindlimbs of C57/BL6 mice were subjected to 3h ischemia and 4 wks reperfusion via placement of release of a tourniquet at a greater trochanter. Treatment of Dexamethasone (Dex, 1 mg/kg/day) for 4 weeks had a strong anti‐inflammatory effect but did not improve muscle contraction. However, treatment of Dex at the first 2 weeks induced a mild anti‐inflammatory effect and had the recovery of muscle contraction. Additionally liposome‐Dex (14 mg/kg) was bolus‐intravenously injected before IR due to severe side effects of Dex. Live imaging showed that this drug had a high target in IR muscles and stayed in the muscles at the first 2 wks of IR. Liposome‐Dex not only decreased expression of IL‐1β and NFkB‐p50, but also improved muscle contraction, compared to IR group. These data suggest that anti‐inflammatory effect of liposome‐Dex in early stage of IR is beneficial to muscle function recovery from IR without Dex‐associated side effects.