Peripheral regional anesthesia alleviates skeletal muscle injury and inflammation caused by acute compartment syndrome by inhibiting PI3K/AKT/NF-kB pathway and regulating macrophage polarization.

BACKGROUND

Acute compartment syndrome (ACS) is a serious complication of tibial fractures that can cause muscle necrosis. Although the protective effects of peripheral regional anesthesia (PRA) in ACS have been documented recently, the exact mechanism is still unknown. This research aimed to investigate the therapeutic efficacy and potential mechanism of PRA in skeletal muscle injury caused by ACS.

METHODS

Sprague-Dawley (SD) rats were randomly divided into three groups (fracture group, FG; ACS group, AG; ACS + PRA group, PG). We established the ACS model and performed PRA guided by ultrasound. We assessed edema and blood flow of the affected limb, as well as apoptosis and fibrosis of skeletal muscle. RNA sequencing of skeletal muscle was used to observe enrichment analysis. Then, immunofluorescence and western blot were used to verify the expression of key proteins.

RESULTS

PRA not only can significantly reduce edema, fibrosis and apoptosis of skeletal muscle caused by ACS but also it can alleviate ischemia. The data of RNA sequencing showed that PRA can ameliorate skeletal muscle injury by inhibiting PI3K/AKT/NF-kB pathway and we found that the protective role of PRA in skeletal muscle may be related to macrophage polarization, which was verified by immunofluorescence analyses. After adding the agonist of PI3K/AKT/NF-kB pathway, the beneficial effects of PRA were attenuated.

CONCLUSION

Our research indicates that PRA may effectively reduce skeletal muscle damage and inflammation caused by ACS by inhibiting the PI3K/AKT/NF-kB pathway and regulating macrophage polarization, offering a new therapeutic strategy for ACS.