Triptolide improves motor dysfunction in rats following spinal cord injury / 中国组织工程研究

ABSTRACT

BACKGROUND: One of the main causes of high disability rate of secondary spinal cord injury is oxidative stress and inflammatory response. How to suppress secondary spinal cord injury is a hot topic of current research. OBJECTIVE: To explore the improvement effect of triptolide on motor dysfunction after spinal cord injury and its possible mechanism. METHODS: Forty-eight healthy male Sprague-Dawley rats were randomly divided into sham operation group, spinal cord injury group and triptolide group, 16 rats in each group. The modified Allen method was used to establish the rat spinal cord injury model. Rats in the triptolide group received intraperitoneal injection of triptolide (0.1 mg/kg per day) 30 minutes after spinal cord injury. Both the sham operation group and spinal cord injury group were given the same amount of normal saline containing 1% dimethyl sulfoxide via the same route for 10 consecutive days. The sham operation group only underwent laminectomy without damaging spinal cord. Basso-Beattie-Bresnahan scoring method was used to evaluate hindlimb function of Sprague-Dawley rats at 7, 14, 21, 28, and 35 days after surgery. The thoracic spinal cord (T8-11) of the rats was collected on the 10th day after surgery for histological detection, western blot, and real-time quantitative PCR analysis. RESULTS AND CONCLUSION: The behavioral scores in the spinal cord injury group and triptolide group increased with increasing days from injury, and the behavioral scores in the triptolide group were significantly higher than that in the spinal cord injury group at 14, 21, 28, and 35 days after surgery (P < 0.05). Hematoxylin-eosin staining results of the T8-11 sections at 10 days after surgery revealed severe edema, bleeding, and inflammatory cell infiltration in the longitudinal section of the thoracic spinal cord core area of the spinal cord injury group, and these abnormalities could be significantly reduced by triptolide treatment (P < 0.05). RT-PCR results showed that compared with the spinal cord injury group, the expression levels of tumor necrosis factor-α, p-STAT3 and p-JAK2 mRNAs in the spinal cord was significantly decreased (P < 0.05), and the levels of superoxide dismutase and catalase mRNAs were significantly increased in the triptolide group (P <0.05). Findings from this study confirm that intraperitoneal injection of triptolide can moderately improve motor dysfunction after spinal cord injury. Its mechanism may be related to the abnormal activation of JAK/STAT signaling pathway regulated by triptolide.