支气管肺发育不良不同时期基质金属蛋白酶、基质金属蛋白酶特异性组织抑制物及核转录因子κB表达变化

Expression Level of Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinases and Activity of Nuclear Factor Kappa B in Different Phases of Bronchopulmonary Dysplasia

目的研究基质金属蛋白酶(MMP-9)及其抑制剂基质金属蛋白酶特异性组织抑制物(TIMP-1)在支气管肺发育不良(BPD)患儿肺组织中的表达,探讨细胞外基质降解在BPD发病机制中的作用;同时进行肺组织核转录因子(NF—κB)活性研究,阐明MMP-9转录机制的调控。方法收集我院新生儿病房死亡患儿尸检肺组织标本共29例,分别行肺组织病理染色、MMP-9、TIMP-1和NF-κB免疫组织化学染色。根据临床诊断和尸检病理诊断分为2组:1.肺透明膜病(HMD)或BPD组: 25例,依据Dik分期标准,按死亡时日龄将其分为4期,急性期(11例)、再生期(7例)、过渡期(2例)和慢性期(5例);2.对照组: 即无肺部疾病者4例。结果BPD组MMP-9表达明显高于对照组,且BPD慢性期MMP-9/TIMP-1比值明显降低(P< 0.05);细胞核内NF—κB与MMP-9表达强度呈正相关(r=0 7419)。结论MMP-9/TIMP-1表达失衡造成细胞外基质降解发生变化为BPD的重要发病机制之一;NF—κB在上调MMP-9表达中起关键作用。

Objective To explore the expression level of matrix metalloprotemases( MMP-9), tissue inhibitor of metailoproteinases (TIMP-1) and the activity of nuclear factor-κB(NF-κB)in the lung tissue of infants with bronchopulmonary dysplasia (BPD)and the extracellular matrix degradation in the pathogenesis of BPD so as to explain the transcription mechanism of MMP-9. Methods Autopsy lung specimens were obtained from 29 infants hospitalized in NICU. Lung tissue HE staining and MMP-9, TIMP-1 and NF-κB were examined by immunohistochemistry. Among the 29 cases, 25 cases developed HMD or BPD and 4 cases had no lung disease. According to Dik WA, 11 patients were included in the acute phase, 7 in the regenerative phases, 2 in the transitional phase and 5 in the chronic phase. Results MMP-9 staining intensity increased in BPD group compared with control group. The ratio of MMP-9/TIMP-1 was significantly lower in the chronic phase( P< 0.05) The expression of MMP-9 had positive correlation with NF-κB in the cell nu-clear( r = 0.742).Conclusions The imbalance MMP-9/TIMP-1 plays an important role in the development of BPD. NF-κB can upgrade the expression of MMP-9.