Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs.
Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs.
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DOI：
10.1186/1465-9921-10-19
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发表时间：
2009-03-10
影响因子：
5.8
通讯作者：
Hooper SB
中科院分区：
文献类型：
--
作者：
Wallace MJ;Probyn ME;Zahra VA;Crossley K;Cole TJ;Davis PG;Morley CJ;Hooper SB
支气管肺发育不良（BPD）与极早产儿呼吸机诱导的肺损伤（VILI）密切相关。VILI的最大风险可能发生在出生后的即刻，此时肺表面活性剂缺乏，仍然部分充满液体并且不均匀充气。然而，很少有研究检查了出生后的这段时间，并确定了最初的损伤相关通路被激活。我们的目的是确定是否早期反应基因，结缔组织生长因子（CTGF），富含半胱氨酸-61（CYR 61）和早期生长反应1（EGR 1），迅速诱导VILI早产羔羊和是否通气不同潮气量引起不同的炎症细胞因子和早期反应基因的表达。为了鉴定VILI的早期标志物，早产羔羊（132天胎龄; GA，足月~147天）用损伤性通气策略（VT 20 mL/kg，持续15分钟）复苏，然后轻轻通气（5 mL/kg）15、30、60或120分钟（每种n = 4）。为了确定早期反应基因和炎性细胞因子是否受到不同通气策略的差异调节，将早产羔羊（125 d GA;每组n = 5）从出生起以VT 5（VG 5）或10 mL/kg（VG 10）通气135分钟。肺基因表达水平与年龄匹配的对照胎儿通气前的水平进行了比较。在损伤性通气30分钟内，CTGF、CYR 61和EGR 1肺mRNA水平分别增加~25、50和120倍（p < 0.05）。与对照水平相比，VG 5和VG 10导致CTGF、CYR 61、EGR 1、IL 1-β、IL-6和IL-8 mRNA水平显著增加。CTGF、CYR 61、IL-6和IL-8的表达水平在VG 10中高于VG 5羔羊;尽管仅IL-6和CYR 61 mRNA水平达到显著性。CTGF、CYR 61和EGR 1可能是肺损伤的新的早期标志物，从出生开始使用相对较低潮气量的机械通气可能比使用较高潮气量的损伤更小。
Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression. To identify early markers of VILI, preterm lambs (132 d gestational age; GA, term ~147 d) were resuscitated with an injurious ventilation strategy (VT 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a VT of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses. CTGF, CYR61 and EGR1 lung mRNA levels were increased ~25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1-β, IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance. CTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes.
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影响因子：
4.8
作者：
Chen, CC;Mo, FE;Lau, LF
通讯作者：
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DOI：
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DOI：
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DOI：
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发表时间：
1998-08-01
影响因子：
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