高体积分数氧致慢性肺疾病新生大鼠肺组织基质金属蛋白酶-13和基质金属蛋白酶组织抑制剂-1表达的意义  

Temporal Expressions and Significances of Matrix Metalloproteinases-13 and Tissue Inhabitor of Metalloproteinases-1 in Lung of Newborn Rats with Hyperoxia Induced Chronic Lung Disease

作　　者：陈宁[1] 刘雪雁[1] 那磊[2] 薛辛东[1] 

机构地区：[1]中国医科大学附属盛京医院儿科,沈阳110004 [2]中国医科大学,九十期七年制沈阳110000

出　　处：《实用儿科临床杂志》2008年第14期1068-1070,共3页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金项目资助(30672253)

摘　　要：目的观察高体积分数氧(高氧)致慢性肺疾病(CLD)新生大鼠肺组织基质金属蛋白酶-13(MMP-13)和基质金属蛋白酶组织抑制剂-1(TIMP-1)的动态变化,探讨CLD发病与MMPs的关系。方法将新生大鼠于出生24h内随机分为高氧组和对照组,每组各40只;于出生第1、3、7、14、21天处死,留取其肺组织,苏木素-伊红(HE)、Masson染色,酶联免疫吸附法检测其Ⅰ型胶原(ColⅠ)表达;免疫组织化学法检测其肺组织MMP-13和TIMP-1的表达。结果随高氧暴露时间的延长,新生大鼠肺组织光镜下表现为次级隔数目和肺泡数目减少,终末气腔扩张,肺泡间隔增宽。随高氧暴露时间的延长,肺组织ColⅠ型胶原蛋白沉积在第14天较对照组显著增加(P<0.01),第21天差异更为显著(P<0.001)。MMP-13和TIMP-1主要在上皮细胞、内皮细胞、间质细胞、肺泡巨噬细胞等细胞胞质中表达;第21天高氧组肺组织MMP-13表达与对照组比较明显下降(P<0.05),其余时间点二组比较无明显差异(Pa>0.05),TIMP-1表达随高氧暴露时间延长逐渐增加,高氧组第14、21天较对照组表达均显著增加(Pa<0.01)。结论高氧致CLD新生大鼠肺组织存在MMP-13/TIMP-1表达失衡,是高氧后期以ColⅠ为代表细胞外基质异常沉积的关键。Objective To observe temporal expression of matrix metalloproteinases（ MMP - 13 ） and tissue inhibitor of metalloproteina- ses - 1 （TIMP - 1 ） in lung of newborn rats with hyperoxia induced chronic lung disease （CLD） ,and to explore the relationship of CLD with MMPs. Methods The neonatal rats within 24 hours after birth were randomly divided into hyperoxia - exposed group （ n = 40） and control group （n = 40）. On postnatal 1,3,7,14 and 21 days,lung tissue of rats in 2 groups were collected. Lung histological changes were evaluated by hematoxylin and eosin and Masson stain;Collagen I was detected by enzyme linked immunoadsorbent assay;MMP- 13 and TIMP - 1 were identifide by immunohistocbemistry. Results Exposured to hyperoxia enviroment for 21 days,tbe number of alveolar decreased,terminal air space enlarged,inter - alveolar septa thickened,and deposition of interstitial collagen fibers. On 14 and 21 days,collagen I in the lung of hy- peroxia - exposed group increased significantly compared with that of control group（ P 〈 0.01,0. 001 ）. MMP - 13 and TIMP - 1 were expressed in cytoplasmic of epithelial cells and microvascular endothelial cells, interstitial cells and pulmonary macrophages. Compared with con- trol group, the expression of MMP- 13 in the lung of hyperoxia -exposed group kept the same level on 1,3,7,14 day（ Pa ~ 0.05 ）, obviously decreased on 21 clay （ P 〈 0.05 ） ; with time of hyperoxia exposure extended,＇lIMP - 1 increased continuously, significantly enhanced on 14,21 day（Pa 〈 0.01 ）. Conclusions There exist imbalances of MMP - 13/TIMP - 1 in lung of newborn rats with hyperoxia induced CLD. And which maybe play an important role in extracellular matrix abnormal deposition at the later phase of hyperoxia exposure. J Appl Clin Pediatr, 2008,23 （14） ： 1068 - 1070

关 键 词：慢性肺疾病 高体积分数氧 Ⅰ型胶原 基质金属蛋白酶-13 基质金属蛋白酶组织抑制剂-1 

分 类 号：R563.9[医药卫生—呼吸系统]