Salvianic Acid A Sodium Promotes the Recovery of Motor Function After Spinal Cord Injury in Rats by Reducing Microglia Inflammation through Regulating MIP2/Vdac1/Ndufa12 Signaling Axis

Orthop Surg. 2020 Dec;12(6):1971-1979. doi: 10.1111/os.12808. Epub 2020 Oct 20.

Abstract

Objective: To clarify the effects on and the mechanism of salvianic acid A sodium (SAAS) in the recovery of motor function after spinal cord injury.

Methods: In vivo and in vitro experiments were carried out in this research to determine the effects of SAAS on tissue damage, neuron survival, microglia polarization, and inflammation after spinal cord injury (SCI). Differentially expressed genes treated with SAAS were screened by transcriptome sequencing, and the molecular mechanism was investigated simultaneously.

Results: The results revealed that SAAS could promote type M2 polarization of microglia and reduce the proportion of type M1. In this way, it reduced the secretion and expression of inflammatory factors. Compared with Lipopolysaccharides(LPS), 345 genes were upregulated and 407 genes were downregulated in the LPS + SAAS treatment group. In the SAAS group, expression levels of Ndufa12, IL-6, TNF-α, and Vdac1 were significantly reduced, while a marked elevation was found in MIP2. In addition, results found in an animal model showed that SAAS could obviously facilitate motor function recovery of mice after spinal cord injury, and it had a good protective effect on spinal cord tissue and neuron cells.

Conclusion: As a result, the present study clarified both the protective effect of SAAS on neurons after spinal cord injury and the anti-inflammatory effect of microglia, which is expected to serve as a theoretical basis for clinical treatment.

Keywords: Microglia; Motor function; SAAS; SCI.

MeSH terms

  • Animals
  • Chemokine CXCL2 / metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Gene Expression / drug effects
  • Inflammation / drug therapy*
  • Lactates / pharmacology*
  • Male
  • Microglia / drug effects*
  • NADPH Dehydrogenase / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / drug therapy*
  • Up-Regulation
  • Voltage-Dependent Anion Channel 1 / metabolism*

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Lactates
  • Vdac1 protein, mouse
  • 3,4-dihydroxyphenyllactic acid
  • Voltage-Dependent Anion Channel 1
  • NADPH Dehydrogenase