The dynamic expression and internal relationship of matrix metalloproteinase-9, interleukin-1β and tissue inhibitor of metalloproteinase-1 in hypoxic-ischemic injury of neonatal rats / 中国小儿急救医学

ABSTRACT

Objective:To investigate the expression levels and internal relations of matrix metalloproteinase-9(MMP-9), interleukin(IL)-1β and tissue inhibitor of metalloproteinase-1(TIMP-1) within 24 h after cerebral hypoxia and ischemia(HI) in neonatal rats.Methods:SD rats aged 7 days were randomly divided into HI group( n=40), and sham operation group(sham group, n=40). The HI models were established and divided into 5 subgroups with those at 8 cases in each group at 5 postoperative time points(0, 4, 8, 12, 24 h). Pathological changes of cerebral cortex were observed by HE staining, and the expressions of MMP-9, IL-1β and TIMP-1 were detected by Western blot and RT-PCR.In addition, the hypoxia models of mouse hippocampal neuron HT22 cells were established.With adding MMP-9 inhibitor and MMP-9 agonist, the relations among MMP-9, IL-1β and TIMP-1 were further confirmed. Results:Slight nuclear abnormalities and cell body swelling occurred in cerebral cortex at 4 h after HI, and neuronal eosinophilic changes were most obvious at 12 h. Compared with those at 8 h and 12 h, the expressions of MMP-9 and IL-1β at protein and mRNA level significantly increased at 24 h after HI( P<0.01). While MMP-9 inhibitor was added to HT22 cells under hypoxia at 4 h, IL-1β mRNA expression was down-regulated. Conclusion:In the early stage of hypoxic ischemic encephalopathy in newborn rats, the expressions of MMP-9 and TIMP-1 are time-dependent.Inhibition of MMP-9 expression could reduce the level of Interleukin-1β.