基质金属蛋白酶-9和肿瘤坏死因子α在大鼠光气吸入性肺损伤中的表达及意义

Expression and Effect of MMP-9 and TNF-α in Rats with Phosgene-Induced Acute Lung Injury

目的：探讨基质金属蛋白酶-9（MMP-9）和肿瘤坏死因子α（TNF-α）在大鼠光气吸入性肺损伤中的表达及意义。方法：SPF级SD大鼠（180~220g）50只,随机分为空气对照组和光气暴露组。建立大鼠光气吸入性肺损伤动物模型,并分别于光气染毒后2、46、、8h采用实时定量逆转录聚合酶链反应（RT-PCR）方法测定MMP-9mRNA在肺组织中的表达含量,酶联免疫吸附试验（ELISA）法测定支气管肺泡灌洗液（BALF）中的TNF-α含量,同时对肺湿/干质量比,支气管肺泡灌洗液（BALF）中蛋白含量、中性粒细胞数以及肺组织病理学改变进行动态监测和对比分析。结果：与空气对照组相比,光气暴露组肺组织出现水肿、出血、炎性细胞浸润,随时间延长进一步加重。光气暴露组肺湿/干质量比值,BALF中蛋白含量、TNF-α含量、中性粒细胞计数均明显高于空气组（P〈0.05）;光气暴露各组MMP-9mRNA表达水平和BALF中MMP-9的表达明显高于空气对照组,随时间延长肺水肿加重（P〈0.01）。结论：基质金属蛋白酶的过度激活和表达及其与炎症因子相互影响在光气肺损伤过程中发挥重要的作用。

Objective：To investigate the role of matrix metalloproteinase-9（MMP-9）and TNF-α in the pathogenesis of acute lung injury induced by phosgene poisoning.Methods： Fifty Sprague Dawley（SD）rats were randomly separated into two groups,the control group and the experiment groups（2h,4h,6h,8h after phosgene poisoning）.Sacrifice the experiment rats 2h,4h,6h,8h after phosgene poisoning.Wet and dry ratio of the lung（wet∕dry） and protein concentration,TNF-α and MMP-9 concentration and polymorphonuclear neutrophils in bronchoalveolar lavage fluid（BALF） were recorded,histopathology of the lung was observed under the light scope,and the quantitation of MMP-9mRNA was determined by Real time RT-PCR.Results： Compared to control group,pulmonary edema and inflammatory cells infiltrating appeared in the experiment group rats.Wet-to-dry lung weight ratio,protein concentration,TNF-α concentration and polymorphonuclear neutrophils count in BALF were higher in phosgene poisoning group compared to control group.（P0.05）.Acute lung injury caused by phosgene was accompanied with increased expression of MMP-9mRNA in lung tissues（P0.01）,which was correlated with lasting of time and aggravation of lung injury.Conclusions： MMP-9 and its relation with inflammatory factors such as TNF-α play an important role in the development of phosgene-induced acute lung injury in rats.