<p class="jove_content"&gt;目前的研究是由国家心脏，肺和血液研究所资助以R01 - HL0921，R01 - DK083385和R01HL098294港元Eltzschig，1K08HL102267 - 01 T。Eckle，麻醉教育和研究资助到T Eckle基金会支持香港Eltzschig，和美国心脏协会授予T. Eckle和香港Eltzschig和德意志研究联合会（DFG）的研究奖学金M. KOEPPEN。</p

总论： 所有操作都应该执行下一个堂堂正正的解剖显微镜（奥林巴斯，与Z轴与曲柄STU2支架臂支架邮政SZX10），并通过使用一个手术凝固剂（11）。实验组应尽量可能在年龄和体重相匹配，以确保结果的可比性。 ，体温，血压，麻醉和流体管理应稳定。 1。麻醉和气管准备<ol><li>使用至少10周龄的C57BL / 6小鼠，并有22-25克的身体使用的剂量70毫克/公斤体重的IP（6）戊巴比妥钠诱导麻醉。保持约10毫克/公斤/小时戊巴比妥钠麻醉。小心过量，因为这可能会显着降低血压。给药苯巴比妥 - 即使小时，可导致血浆中的严重增加。 </li><li>麻醉诱导后，在仰卧位表使用磁带和一期缝合固定脚踝上，下肢的安全小鼠。不要使用牙齿相同的头部。足够的限制是很重要的一个成功的插管和手术很好的控制。手术前，盖与矿物油鼠标，以减少鼠毛过敏的风险。为了确保体温保持稳定，与市售食品保鲜膜覆盖的小鼠。 </li><li>广场小鼠加热温度控制表（RT，埃芬博格，慕尼黑，德国）与直肠温度计探头连接到热反馈控制器，以保持体温在37 ° C。 </li><li>暴露的气管手术。解剖的结缔组织和地方两个3.0丝的手术缝合线（美国哈佛仪器，）每10厘米长气管下面的气管外侧和背两面。缝线应相距约1厘米。 </li><li>小心切开气管3 - 4毫米以下使用麦弗逊式Vannas剪刀（8厘米，直叶片;世界精密仪器，美国）之间的两个圆形软骨喉。确保不引起出血，因为这可能会混淆的结果参数。 </li><li>执行气管插管，使用钝的聚乙烯套管（Insyte 22G，Beckton Dickinson公司，美国）。聚乙烯套管插入进气管在一个85度角的尖端。然后倾斜套管，所以它是在与气管管腔。慢慢推进管进一步下降气管套管尖端直到消失在胸部光圈。在这个位置上，注视两种手术丝放置气管（见1.4）的背侧缝合管。 </li></ol> 2。呼吸机相关性肺损伤的技术<ol><li>呼吸机连接管。为了诱导肺损伤，我们使用一个压力控制通风技术，通过使用来自西门子（DRE兽医，美国）伺服900 ℃。动物将使用一个FIO 2 = 1.0 45毫巴，频率80次/ min，吸气峰压0-3毫巴的压力呼气末正压通风。灵感到期的比例应是1:1。尽管伺服900℃是人类呼吸机内置的事实，其压力控制呼吸机设置使用作品的优秀小鼠的通风。 </li><li>心率监测心电图（如惠普，blingen乙，德国）。确保心率不低于400。我们应该看到一个心轴右移，当机械通气作为胸腔内压力增加后，增加肺动脉压力的标志提起。如果鼠标的发展心动过缓，检查温度和麻醉剂的剂量/浓度。 Xylacin /氯胺酮麻醉诱导烂熟于心了250元/分钟，因此不推荐。 </li><li>应用适当的补液。一个输液生理盐水0.1毫升/小时通过动脉或静脉导管之前进行通风，以确保足够的静脉备案。由于高的通风压力，静脉回流到心脏受损，可能导致的平均动脉压的关键下降。另外，500μL生理盐水静脉推注可给予手术前的IP。 </li><li>放置在颈动脉血压（27）的连续录音导管。将手臂向身体，然后再开始解剖动脉。颈动脉是通过钝性分离气管肌肉暴露。经过进一步的接触和小心避免任何组织创伤（尤其是迷走神经），导管插入使用两个缝线和一个小钳（37）的船只。这将会使一个较长段的动脉。放置在颈动脉非常结扎。将较大的钳缝合结束，获得紧张或注视日发送缝合表使用磁带。将另一个周围动脉缝合动脉解剖的末端。在这里，放在一个小卡子。使用微型剪刀剪一小对角线开放到动脉。与罚款钳（杜蒙，WPI），保持开放和推进适当大小的导管，用你的手/钳。您的第二缝合打了一个结，安全的动脉。松开夹子，并进一步推进导管。安全与几节和磁带的导管。另外，颈内动脉导管可在实验结束的地方，收集动脉血血气分析样品。 </li></ol> 3。组织样本的恢复经过3个小时的机械通气后，样品的采集，评估肺损伤的的程度。我们建议收集brochnoalveolar灌洗液（BAL），动脉血和肺组织。 <ol><li>在实验结束后获取BAL液。深化麻醉后，气管导管冲洗1毫升磷酸缓冲液（PBS）。流体应保持三秒钟之前，它是通过连接注射器回收气管/肺。的BAL管理单元冷冻在液氮中，并储存于-80 ° C，作进一步的分析。要知道，回收的量可能会大大超过1毫升。 </li><li>在实验结束后进行血气分析。为了做到这一点，切口应低于胸骨。保持与产钳和程度的切口沿肋骨胸骨。接下来，膈肌切开边缘，从肋骨被切断。现在有一个较低的光圈到胸部开放的观点。提起胸骨钳和开放的胸部长在右侧和左侧的削减（尽可能横向），完整的前胸部墙被打开的病房。这应该做的，而实验动物仍然是机械通气。左心室被刺破了27 ½ G针和动脉血分析使用的i - STAT系统（美国雅培）。如果应进行动脉血气分析，不能取得一个平衡，因为这将是一个显着的混杂因素的结果。 </li><li>除了上述方法，可以收集通过颈内动脉导管动脉血液样本。然而，这项工作应获得的BAL前。 </li><li>海关肺部整块拉起的心脏和削减气管。有准备吸收血液中的一块组织，使手术部位可见。拉心在腹部的方向和沿脊柱小心切调动一切胸机关。切断主动脉，取出胸腔器官和它们放置在一个干净的手术台。 </li><li>切去心脏和大血管的组织样本。确保没有胸腺组织仍然附着在肺。分开个别管和管理单元冻结的剪刀和地方的肺部。贮存于-80 ° C，作进一步的分析。 </li></ol> 4。肺损伤的测量我们建议使用以下的结果参数评估肺损伤的程度：执行白蛋白酶联免疫吸附（Bethyl实验室，美国）和一个过氧化物酶（MPO）ELISA试剂盒（美国）Hycult生物技术，以评估屏障功能障碍的程度和炎症金额在BAL液中的细胞。执行一个MPO ELISA也形成肺组织。如果湿干比来衡量，我们没有获得BAL液和肺循环是没有刷新（见3.3）。测量切除后肺的重量。然后，肺部冻干48 h和肺组织再次测量。然后湿干比是衡量每毫克干组织的水（5）毫克。 <img src="/files/ftp_upload/2525/2525fig1.jpg" alt="图1" /> 图1。VILI 的小鼠BAL中的蛋白质含量与苯巴比妥麻醉，机械通气是制定和小鼠通风使用压力控制设置（吸气压力45毫巴，积极exspiratory最终压力3毫巴，100％的启发氧浓度）。后0，1，2和3小时的通风平衡是收获和使用bicinchoninic酸法（BCA法测定）的蛋白质含量进行了量化。蛋白质含量的相对变化是标准化方式显示为0小时的通风（N = 4每个组，*表示P &lt;0.05与对照组比较，平均± SEM ）

<ol>
	<li>Eckle, T., Faigle, M., Grenz, A., Laucher, S., Thompson, L. F., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A2B+adenosine+receptor+dampens+hypoxia-induced+vascular+leak.">A2B adenosine receptor dampens hypoxia-induced vascular leak.</a> Blood. 111, 2024-2035 (2008).</li><li>Eckle, T., Fullbier, L. G. r. e. n. z., A, ., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Usefulness+of+pressure-controlled+ventilation+at+high+inspiratory+pressures+to+induce+acute+lung+injury+in+mice.">Usefulness of pressure-controlled ventilation at high inspiratory pressures to induce acute lung injury in mice.</a> Am J Physiol Lung Cell Mol Physiol. 295, 718-724 (2008).</li><li>Eckle, T., Fullbier, L., Wehrmann, M., Khoury, J., Mittelbronn, M., Ibla, J., Rosenberger, P., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+ectonucleotidases+CD39+and+CD73+in+innate+protection+during+acute+lung+injury.">Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury.</a> J Immunol. 178, 8127-8137 (2007).</li><li>Eckle, T., Grenz, A., Kohler, D., Redel, A., Falk, M., Rolauffs, B., Osswald, H., Kehl, F., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+evaluation+of+a+novel+model+for+cardiac+ischemic+preconditioning+in+mice.">Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice.</a> Am J Physiol Heart Circ Physiol. 291, 2533-2540 (2006).</li><li>Eckle, T., Grenz, A., Laucher, S., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A2B+adenosine+receptor+signaling+attenuates+acute+lung+injury+by+enhancing+alveolar+fluid+clearance+in+mice.">A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice.</a> J Clin Invest. 118, 3301-3315 (2008).</li><li>Eckle, T., Krahn, T., Grenz, A., Kohler, D., Mittelbronn, M., Ledent, C., Jacobson, M. A., Osswald, H., Thompson, L. F., Unertl, K., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardioprotection+by+ecto-5'-nucleotidase+(CD73)+and+A2B+adenosine+receptors.">Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors.</a> Circulation. 115, 1581-1590 (2007).</li><li>Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenosine:+an+old+drug+newly+discovered.">Adenosine: an old drug newly discovered.</a> Anesthesiology. 111, 904-915 (2009).</li><li>Eltzschig, H. K., Eckle, T., Mager, A., Kuper, N., Karcher, C., Weissmuller, T., Boengler, K., Schulz, R., Robson, S. C., Colgan, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ATP+release+from+activated+neutrophils+occurs+via+connexin+43+and+modulates+adenosine-dependent+endothelial+cell+function.">ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function.</a> Circ Res. 99, 1100-1108 (2006).</li><li>Eltzschig, H. K., Ibla, J. C., Furuta, G. T., Leonard, M. O., Jacobson, K. A., Enjyoji, K., Robson, S. C., Colgan, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coordinated+adenine+nucleotide+phosphohydrolysis+and+nucleoside+signaling+in+posthypoxic+endothelium:+role+of+ectonucleotidases+and+adenosine+A2B+receptors.">Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors.</a> J Exp Med. 198, 783-796 (2003).</li><li>Eltzschig, H. K., Kohler, D., Eckle, T., Kong, T., Robson, S. C., Colgan, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+role+of+Sp1-regulated+CD39+in+hypoxia/ischemia+protection.">Central role of Sp1-regulated CD39 in hypoxia/ischemia protection.</a> Blood. 113, 224-232 (2009).</li><li>Frick, J. S., MacManus, C. F., Scully, M., Glover, L. E., Eltzschig, H. K., Colgan, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+adenosine+A2B+receptors+to+inflammatory+parameters+of+experimental+colitis.">Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis.</a> J Immunol. 182, 4957-4964 (2009).</li><li>Grenz, A., Eckle, T., Zhang, H., Huang, D. Y., Wehrmann, M., Kohle, C., Unertl, K., Osswald, H., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+a+hanging-weight+system+for+isolated+renal+artery+occlusion+during+ischemic+preconditioning+in+mice.">Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice.</a> Am J Physiol Renal Physiol. 292, 475-485 (2007).</li><li>Grenz, A., Osswald, H., Eckle, T., Yang, D., Zhang, H., Tran, Z. V., Klingel, K., Ravid, K., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Reno-Vascular+A2B+Adenosine+Receptor+Protects+the+Kidney+from+Ischemia.">The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia.</a> PLoS Medicine. 5, e137-e137 (2008).</li><li>Grenz, A., Zhang, H., Eckle, T., Mittelbronn, M., Wehrmann, M., Kohle, C., Kloor, D., Thompson, L. F., Osswald, H., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protective+role+of+ecto-5'-nucleotidase+(CD73)+in+renal+ischemia.">Protective role of ecto-5'-nucleotidase (CD73) in renal ischemia.</a> J Am Soc Nephrol. 18, 833-845 (2007).</li><li>Grenz, A., Zhang, H., Hermes, M., Eckle, T., Klingel, K., Huang, D. Y., Muller, C. E., Robson, S. C., Osswald, H., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+E-NTPDase1+(CD39)+to+renal+protection+from+ischemia-reperfusion+injury.">Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury.</a> FASEB J. 21, 2863-2873 (2007).</li><li>Grenz, A., Zhang, H., Weingart, J., von Wietersheim, S., Eckle, T., Schnermann, J. B., Kohle, C., Kloor, D., Gleiter, C. H., Vallon, V., Eltzschig, H. K., Osswald, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lack+of+effect+of+extracellular+adenosine+generation+and+signalling+on+renal+erythropoietin+secretion+during+hypoxia.">Lack of effect of extracellular adenosine generation and signalling on renal erythropoietin secretion during hypoxia.</a> Am J Physiol Renal Physiol. , (2007).</li><li>Haeberle, H. A., Durrstein, C., Rosenberger, P., Hosakote, Y. M., Kuhlicke, J., Kempf, V. A., Garofalo, R. P., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxygen-independent+stabilization+of+hypoxia+inducible+factor+(HIF)-1+during+RSV+infection.">Oxygen-independent stabilization of hypoxia inducible factor (HIF)-1 during RSV infection.</a> PLoS ONE. 3, e3352-e3352 (2008).</li><li>Hart, M. L., Gorzolla, I. C., Schittenhelm, J., Robson, S. C., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=SP1-dependent+induction+of+CD39+facilitates+hepatic+ischemic+preconditioning.">SP1-dependent induction of CD39 facilitates hepatic ischemic preconditioning.</a> J Immunol. 184, 4017-4024 (2010).</li><li>Hart, M. L., Henn, M., Kohler, D., Kloor, D., Mittelbronn, M., Gorzolla, I. C., Stahl, G. L., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+extracellular+nucleotide+phosphohydrolysis+in+intestinal+ischemia-reperfusion+injury.">Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury.</a> FASEB J. 22, 2784-2797 (2008).</li><li>Hart, M. L., Jacobi, B., Schittenhelm, J., Henn, M., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cutting+Edge:+A2B+Adenosine+receptor+signaling+provides+potent+protection+during+intestinal+ischemia/reperfusion+injury.">Cutting Edge: A2B Adenosine receptor signaling provides potent protection during intestinal ischemia/reperfusion injury.</a> J Immunol. 182, 3965-3968 (2009).</li><li>Hart, M. L., Kohler, D., Eckle, T., Kloor, D., Stahl, G. L., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+treatment+of+mouse+or+human+blood+with+soluble+5'-nucleotidase+inhibits+platelet+aggregation.">Direct treatment of mouse or human blood with soluble 5'-nucleotidase inhibits platelet aggregation.</a> Arterioscler Thromb Vasc Biol. 28, 1477-1483 (2008).</li><li>Hart, M. L., Much, C., Gorzolla, I. C., Schittenhelm, J., Kloor, D., Stahl, G. L., Eltzschig, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extracellular+adenosine+production+by+ecto-5'-nucleotidase+protects+during+murine+hepatic+ischemic+preconditioning.">Extracellular adenosine production by ecto-5'-nucleotidase protects during murine hepatic ischemic preconditioning.</a> Gastroenterology. 135, 1739-1750 (2008).</li><li>Hart, M. 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本研究描述了一个执行呼吸机诱导的小鼠肺损伤的技术。这个模型表明由于高压通风的高度重复性的伤害。考虑研究小鼠急性肺损伤的调查可能会受益于这种模式。

<table border="1"><tbody><tr><th>试剂名称</th><th>公司</th><th>目录编号</th><th>评论（可选） </th></tr><tr><td>戊巴比妥钠（致命加） </td><td> Vortech药业LS，有限公司， </td><td> VPL 9372 </td><td> 4mg/mL在生理盐水</td></tr><tr><td> Insyte 22政</td><td> Beckton迪金森</td><td> N / A </td><td></td></tr><tr><td>缝合，丝绸4.0 </td><td>哈佛器械</td><td> 517698 </td><td></td></tr><tr><td>缝合后，普理灵8.0 </td><td>美国爱惜康， </td><td> M8739 </td><td>可重复使用</td></tr><tr><td>西门子900 ° C </td><td>美国指诊兽医， </td><td> ＃336 </td><td>翻新</td></tr><tr><td>解剖显微镜（SZX10） </td><td>奥林巴斯</td><td> N / A </td><td>考虑慷慨的工作距离</td></tr><tr><td>暖气表</td><td> RT，Effenberger，德国</td><td> N / A </td><td>只和单一供应商</td></tr><tr><td>血压装置</td><td>网络意识，公司</td><td> BPM02 </td><td></td></tr><tr><td>我的STAT </td><td>雅培</td><td> N / A </td><td></td></tr></tbody></table>

pressure controlled ventilation to induce acute lung injury in mice

小鼠模型被广泛用于研究不同的器官系统（1-34）的急性损伤。急性肺损伤（ALI）的发生，这与长时间机械通气，有利于重大疾病的发病率和死亡率，并研究新的遗传或药理目标地区的紧张调查（1-3，5，8，26，30，33 -36）。阿里是指急性发作的疾病，从而导致非心源性肺水肿和肺气体交换（36）其后减值。我们已经开发使用的压力控制通气诱发呼吸机相关性肺损伤（2）的ALI小鼠模型。为此，C57BL / 6小鼠麻醉，并进行了气管切开手术是通过机械通气诱导的ALI。小鼠压力控制设置在通风吸气45 mbar的压力峰值超过1 - 3个小时。由于评估结果参数，肺水肿（湿干比），支气管流体白蛋白含量，支气管流体和肺组织髓过氧化物酶含量和肺气体交换（2）。使用这种技术，我们可以证明，这足以引起急性肺部炎症，并能区分不同的治疗组或基因型（1-3）。因此，这种技术可能会为那些追求在ALI使用一种遗传性的方法在小鼠基因靶向缺失的分子机制的研究人员很有帮助。

Watch this Scientific Journal Video about Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice at JoVE.com

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

一个呼吸机诱导肺损伤的小鼠模型是一个重要的工具，研究急性肺损伤<em&gt;在体内</em&gt;。在这里，我们报告一件容易的适用<em&gt;原位</em&gt;模型使用高压机械通气诱发急性肺衰竭的急性肺伤害。

压力控制通气诱导小鼠急性肺损伤

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

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18.1K 次观看.  University of Colorado. 一个呼吸机诱导肺损伤的小鼠模型是一个重要的工具，研究急性肺损伤在体内。在这里，我们报告一件容易的适用原位模型使用高压机械通气诱发急性肺衰竭的急性肺伤害。