Neuroprotective Effect and Mechanism of Astragalus Injection on Acute Spinal Cord Injury in Rats

  OBJECTIVE   To explore the neuroprotective function of Astragalus injection on acute spinal cord injury (SCI) in rats and its mechanism based on apoptosis signaling pathway.

  METHODS   40 healthy male SD rats were randomly divided into sham operation group, SCI group, Astragalus injection low dose group (1 mL · kg^-1), Astragalus injection medium dose group (2 mL · kg^-1) and Astragalus injection high dose group (4 mL · kg^-1). A modified heavy object method was used to construct an acute SCI rat model. The locomotor function of rats was evaluated according to BBB method and Rivlin inclined board test. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of spinal cord tissue. Nissl staining method was used to detect the degree of spinal cord neuronal cell damage. High-throughput transcriptome sequencing to analyze differentially expressed genes. The qPCR method verified the expression level of gene transcription. TUNEL kit was used to detect the apoptosis of spinal cord cells in each group. The expression levels of key proteins in the apoptosis pathway was detected by Western blot.

  RESULTS   The results of BBB score and Rivlin plate test indicated that rats in the model group showed obvious motor dysfunction compared with the sham group. HE staining showed severe pathological changes in spinal cord tissue in the model group. Lighter Nissl staining showed severe neuronal cell damage in the model group. Compared with the sham group, 4 597 genes were differentially expressed in the spinal cord of the model group. The expressions of Fas, TRAIL, Caspase-3, Caspase-8, Caspase-9 and Bax proteins were significantly up-regulated (P < 0.01). Moreover, the protein expressions of Fas apoptosis inhibitor FAIM and anti-apoptotic factor Bcl-2 was significantly reduced (P < 0.01). Compared with the model group, the BBB score and the degree of Rivlin in the Astragalus injection group significantly increased and the degree of tissue lesions becomes smaller (P < 0.05, P < 0.01). As the dose of Astragalus injection increased, the degree of Nissl staining becomes deeper. The injury and apoptosis of spinal cord nerve cells in the Astragalus injection high dose group significantly alleviated (P < 0.01). Compared with the model group, the expressions of FAIM and TRAIL mRNA were significantly expressed in the high-dose Astragalus injection group (P < 0.01), the expressions of Fas, TRAIL, Caspase-3, Caspase-8, Caspase-9 and Bax protein in Astragalus injection groups were inhibited in a dose-dependent manner (P < 0.05, P < 0.01), the protein expressions of FAIM and Bcl-2 were up-regulated (P < 0.01).

  CONCLUSION   Astragalus injection may inhibit the expressions of Fas and TRAIL proteins, thereby regulate the programmed apoptosis of neuronal cells, exert a neuroprotective effect on SCI, improve the degree of SCI, and accelerate the later neuromotor function recovery of obstacles.