Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Proteome Sci. 2010 Jan 29;8:3. doi: 10.1186/1477-5956-8-3.
Although mechanical ventilation (MV) is a major supportive therapy for patients with acute respiratory distress syndrome, it may result in side effects including lung injury. In this study we hypothesize that MMP-9 inhibition by doxycycline might reduce MV-related lung damage. Using a proteomic approach we identified the pulmonary proteins altered in high volume ventilation-induced lung injury (VILI). Forty Wistar rats were randomized to an orally pretreated with doxycycline group (n = 20) or to a placebo group (n = 20) each of which was followed by instrumentation prior to either low or high tidal volume mechanical ventilation. Afterwards, animals were euthanized and lungs were harvested for subsequent analyses.
Mechanical function and gas exchange parameters improved following treatment with doxycycline in the high volume ventilated group as compared to the placebo group. Nine pulmonary proteins have shown significant changes between the two biochemically analysed (high volume ventilated) groups. Treatment with doxycycline resulted in a decrease of pulmonary MMP-9 activity as well as in an increase in the levels of soluble receptor for advanced glycation endproduct, apoliporotein A-I, peroxiredoxin II, four molecular forms of albumin and two unnamed proteins. Using the pharmacoproteomic approach we have shown that treatment with doxycycline leads to an increase in levels of several proteins, which could potentially be part of a defense mechanism.
Administration of doxycycline might be a significant supportive therapeutic strategy in prevention of VILI.
虽然机械通气（MV）是急性呼吸窘迫综合征患者的主要支持性治疗方法，但它可能会导致副作用，包括肺损伤。在这项研究中，我们假设强力霉素对基质金属蛋白酶-9（MMP-9）的抑制作用可能会减少与 MV 相关的肺损伤。我们使用蛋白质组学方法鉴定了大容量通气诱导的肺损伤（VILI）中改变的肺蛋白。40 只 Wistar 大鼠随机分为强力霉素口服预处理组（n = 20）或安慰剂组（n = 20），每组在接受低或高潮气量机械通气前均进行了仪器操作。之后，处死动物并采集肺脏进行后续分析。
与安慰剂组相比，高容量通气组经强力霉素治疗后，机械功能和气体交换参数得到改善。在这两个生物化学分析（大容量通气）组之间有 9 种肺蛋白显示出明显的变化。强力霉素治疗导致肺组织基质金属蛋白酶-9 活性降低，以及晚期糖基化终产物可溶性受体、载脂蛋白 A-I、过氧化物还原酶 II、四种白蛋白分子形式和两种未命名蛋白的水平增加。通过药物蛋白质组学方法，我们发现强力霉素治疗可增加几种蛋白的水平，这些蛋白可能是防御机制的一部分。
强力霉素的给药可能是预防 VILI 的一种重要的支持性治疗策略。
