The expression and significance of HIF-1α and MMP-2 in chronic compressive spinal cord in rat models

English Keywords:Spinal cord injury  Chronic compression  Hypoxia inducible factor-1α  Matrix metalloproteinases-2  Rat

English Abstract:

  【Abstract】 Objectives: To investigate the expression and significance of hypoxia inducible factor-1α(HIF-1α) and matrix metalloproteinases-2(MMP-2) in rats of chronic compressive spinal cord. Methods: Eighty adult SD rats were randomly divided into sham surgery group(n=40) and spinal cord compression group(n=40). A C5 semi-laminectomy was performed in the sham group only, while a water-absorbable polyurethane polymer was implanted into C6 epidural space in the compression group. The Basso Beattie Bresnahan(BBB) score and somatosensory evoked potentials(SEP) were used to evaluate neurological function. The expressions of HIF-1α and MMP-2 in the cervical spinal cords of the sham group and the compression group were detected by immunohistochemistry respectively on the 7th, 28th, 42nd and 70th day after chronic spinal cord compressive injury. The variation of the expression of HIF-1α and MMP-2(IOD value) was analyzed by using the independent samples t-test. The correlation between HIF-1α, MMP-2 and neurological function after spinal cord compression was analyzed by using correlation analysis of paired samples at different time points. Results: At the 7th day, there was no difference of BBB score between the two groups(P>0.05). The latency of SEP was prolonged and the amplitude decreased. Immunohistochemistry showed that HIF-1α expression significantly decreased and MMP-2 expression was significantly increased(P<0.05). BBB score in the compression group had a significant reduction at the 28th day. Compared with the 7th day, the significantly extended latency and decreased amplitude were found in SEP at the 28th day(P<0.05). However, the expression of HIF-1α increased significantly and MMP-2 expression decreased at this time point(P<0.05). At the 42th day, there was no differences in terms of BBB score and SEP between the two groups compared with the 28th day (P>0.05). HIF-1α expression increased and MMP-2 expression decreased(P<0.05). At the 70th day, neurological function in the compression group was significantly improved compared with that at the 28th day. BBB score increased, the latency of SEP was shorter and the amplitude of SEP increased (P<0.05). HIF-1α expression decreased compared with before. The expression of MMP-2 increased, while there was still significantly difference compared with the sham group(P<0.05). The expression of HIF-1α and neurologic function were negatively correlated(r=-0.458, P=0.02); the expression of MMP-2 and neurologic function were positively correlated(r=0.903, P<0.05). Conclusions: There is a certain degree of self-repair in rat models of chronic compressive spinal cord injury. The expression of HIF-1α and MMP-2 is correlated with neurological function change after chronic compressive spinal cord injury.