Glycyrrhizin protects spinal cord and reduces inflammation in spinal cord ischemia–reperfusion injury

Abstract

Objective: Inflammation, which is detrimental to the neurologic defect after ischemia–reperfusion, provides a potential target for therapeutic approach for spinal cord ischemia–reperfusion injury. High mobility group box 1 (HMGB-1) was recently discovered to be a crucial cytokine that mediates the response to infection, injury and inflammation. The present study aimed to gain a deep insight into the neuroprotective effect of glycyrrhizin in the process of ischemia and reperfusion injury in spinal cord of mice. Methods: Spinal cord ischemia was induced in male C57BL/6 mice by occlusion of the thoracic aorta. The experimental groups (n = 6 per group) included sham operation, control (receiving phosphate buffered saline (PBS)) and glycyrrhizin (10 mg/kg, when cross-clamped). Neurologic function was assessed by the motor function score of the hind limbs at 72 hours after reperfusion. Histologic changes were studied using hematoxylin and eosin staining. Expression changes of inflammatory cytokines or their receptors at messenger RNA level or protein level were determined by real-time transcription polymerase chain reaction or enzyme-linked immunosorbent assay at different time points post reperfusion. Nuclear factor κB (NF-κB) activity was examined with Western blotting. Results: Compared with the control group, the glycyrrhizin group showed significantly improved neurologic outcome, reduced apoptosis of motoneurons of spinal anterior horn, decreased the activation of NF-κB and subsequent inflammatory cytokines expression [tumor necrosis factor (TNF) and interleukin 1β (IL-1β)], and alleviated neutrophil infiltration in ischemic spinal cord. HMGB-1 treatment also reduced the expressions of itself. Conclusions: Treatment with glycyrrhizin exerted a neuroprotective effect against spinal cord ischemia–reperfusion injury. The anti-inflammatory effect was believed to be one of the contributing mechanisms. Our findings provided experimental and therapeutic options for the treatment of spinal cord ischemia–reperfusion injury.