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

Abstract

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. Electroacupuncture 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.