Electroacupuncture Alleviates HIF1-α-mediated Early Mitophagy in Spinal Cord Injury

Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment.Hypoxia-inducible factor1α(HIF1-α)can mediate mitochondrial autophagy in neurodegenerative diseases,but the mechanisms are complex and diverse,which need to be further elucidated.Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury,promote long-term neurological function recovery in SCI patients,but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.Objective:Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.Methods:Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method,electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint(EX-B2),with further molecular biology and morphology examined by perfusion.To observe the effect of HIF1-α on local damage repair,the stereotypic injection of Hif1a knockdown virus was performed,and the changes of mitophagy in damaged local area was detected employing Western blotting,real-time fluorescence quantitative PCR,immunofluorescence,transmission electron microscopy and Nissl staining.Results:HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury.Elec-troacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury,reduce cell apoptosis and injury area,promote neuronal survival.Conclusion:Electroacupuncture may serve as a promising strategy for spinal cord injury treatment,by alleviating HIF1-α mediated early mitochondrial autophagy.