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目的:探讨新生乳鼠脑缺氧缺血(hypoxic ischemic，HI)后24 h内基质金属蛋白酶-9(matrix metalloproteinase-9，MMP-9)、白细胞介素-1β(interleukin-1β，IL-1β)和金属蛋白酶组织抑制因子-1(tissue inhibitor of metalloproteinase-1，TIMP-1)的变化规律及关系。方法:7日龄SD乳鼠随机分为HI组(n n＝40)和假手术组(sham组，n n＝40)。建立HI模型，按术后5个时间点(0、4、8、12、24 h)分为5个亚组取脑组织，每组8例。HE染色观察大脑皮质病理变化，Western blot和RT-PCR法检测MMP-9、IL-1β和TIMP-1的表达。此外，制作小鼠海马神经元HT22细胞缺氧模型，加入MMP-9抑制剂和MMP-9激动剂，进一步证实MMP-9、IL-1β和TIMP-1的关系。n 结果:HI后4 h大脑皮质出现轻微的核异常和胞体肿胀，12 h神经元嗜酸性改变最为明显。与8 h、12 h比较，HI后24 h MMP-9和IL-1β蛋白及mRNA表达明显升高(n P<0.01)。HT22细胞缺氧4 h加入MMP-9抑制剂，IL-1β mRNA表达下调。n 结论:新生乳鼠HI早期MMP-9、IL-1β和TIMP-1表达呈时间依赖性，抑制MMP-9表达可降低IL-1β水平。“,”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 n=40), and sham operation group(sham group, n 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.n 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(n P<0.01). While MMP-9 inhibitor was added to HT22 cells under hypoxia at 4 h, IL-1β mRNA expression was down-regulated.n 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.