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目的探讨机械通气致肺损伤大鼠肺组织基质金属蛋白酶(MMP-2和MMP-9)及其组织抑制因子(TIMP-1和TIMP-2)的表达。方法30只健康雄性SD大鼠随机分为3组,麻醉和气管切开及气管内插管后,进行三种方式通气,A组(对照组):保留自主呼吸;B组(小潮气量组):Vr 7ml/kg, 呼吸频率(RR)40次/min;C组(大潮气量组):Vr 40ml/kg,RR 20次/min;B、C组大鼠通气时间均为4 h。测定实验前及通气4 h后PaO2/FiO2、通气4 h后支气管肺泡灌洗液(BALF)中白细胞计数、总蛋白水平及左肺湿重/干重(W/D)比值,并行肺组织病理学检查,RT-PCR检测肺组织MMP-2、MMP-9、TIMP-1和TIMP-2 mRNA的表达;酶谱法分析BALF中MMP-2和MMP-9的活性。结果通气4 h后,与A、B组比较,C组PaO2/FiO2下降,BALF中总蛋白含量、白细胞计数、W/D比值以及MMP-2、MMP-9活性增高,肺组织MMP-2、MMP-9 mRNA表达水平增高,TIMP-1、TIMP-2 mRNA表达水平无明显变化,肺组织有更多的白细胞浸润和肺泡壁结构的破坏。结论大潮气量通气可致大鼠急性肺损伤,MMP-2和MMP-9及TIMP-1和TIMP-2的失衡在其中发挥重要作用。
Objective To investigate the expression of matrix metalloproteinase (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and TIMP-2 in lung tissue of rats with lung injury induced by mechanical ventilation. Methods Thirty healthy male Sprague-Dawley rats were randomly divided into three groups. After anesthesia, tracheotomy and endotracheal intubation, three kinds of ventilation were performed. Group A (control group): spontaneous respiration, group B (small tidal volume) : Vr 7ml / kg and respiratory rate (RR) 40 beats / min; Group C (large tidal volume): Vr 40ml / kg and RR 20 beats / min; The white blood cell count, total protein level and left lung wet weight / dry weight (W / D) ratio in bronchoalveolar lavage fluid (BALF) after PaO2 / FiO2 and 4 h of ventilation were measured before and 4 h after ventilation. The mRNA and protein expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in lung tissue were determined by RT-PCR and the activity of MMP-2 and MMP-9 in BALF were analyzed by zymography. Results Compared with group A and group B, PaO 2 / FiO 2 in group C, total protein in BALF, white blood cell count, W / D ratio and MMP-2 and MMP-9 activity were increased after 4 h of ventilation. The expression of MMP-9 mRNA increased, the expressions of TIMP-1 and TIMP-2 mRNA had no significant changes, the lung tissue had more leukocyte infiltration and the destruction of alveolar wall structure. Conclusions Large tidal volume ventilation can cause acute lung injury in rats. The imbalance between MMP-2, MMP-9, TIMP-1 and TIMP-2 plays an important role.