生长激素对急性肺损伤的影响

目的探讨应激反应阶段生长激素（GH）对脂多糖（LPS）诱导急性肺损伤（ALI）的影响及其机制。方法112只雄性SD大鼠随机均分为ALI组和GH组，按致伤与否及致伤后的观察时间又随机均分为0、0．5、1、2、4、6和24h7个亚组。分别测定大鼠肺泡隔面积密度（PASAD），肺泡隔中性粒细胞数，肺局部肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）水平，肺组织核转录因子-κB（NF-κB）阳性细胞数和肺匀浆液中NF-κB抑制蛋白（I-κBα）含量。结果致伤后ALI组大鼠PASAD进行性增大，肺泡隔中性粒细胞数进行性增多，两者均于6h达峰值，24h基本恢复正常；GH组大鼠PASAD较ALI组同时间点进一步增大，中性粒细胞数增多更明显。ALI组致伤后0．5h肺局部TNF水平开始迅速升高，1h达峰值，其后维持在较高水平，6h后逐渐恢复；致伤后1h IL-6水平开始明显升高，4h达峰值，6h后逐渐恢复；GH组大鼠IL-6水平升高更明显。ALI组致伤后0．5h肺组织中NF-κB阳性细胞数明显增多，4h达峰值，6h开始恢复；GH组大鼠肺组织NF-κB阳性细胞数明显多于ALI组同时间点。伤后0．5h I-κBn含量开始明显下降，4h达最低值，6h后开始回升；GH组大鼠肺组织I-κBa含量下降更明显。相关性分析显示，PASAD、肺组织TNF和IL-6水平及肺泡隔中性粒细胞浸润程度与NF-κB的表达、活化程度呈正相关。结论NF-κB表达、活化在LPS诱导ALI的发病过程中有重要作用。应激反应阶段应用GH可加剧LPS诱导的ALI。其机制与促进肺局部NF-κB表达与活化而加剧肺局部炎症反应有关。     

性激素在急性肺损伤中作用的初步研究

目的 探讨性激素在大鼠急性肺损伤中对肺脏病理变化的可能作用及机制。方法 复制大肠杆菌内毒素脂多糖诱发的雄性大鼠急性肺损伤的模型，切除性腺15d后予以补充雌二醇(1mg／kg)，观察急性肺损伤大鼠的肺组织显微病理变化，并应用免疫组化技术测定肺组织中雌激素受体、孕激素受体的表达及应用放免法测定外周血中的雌二醇、催乳素浓度变化。结果 雌二醇治疗组(A组)大鼠肺组织病理损伤较睾丸切除组(B组)大鼠为轻，B组大鼠肺组织病理损伤较假睾丸切除组(c组)大鼠为轻：A组与B、c组及正常对照组(D组)相比外周血中的雌二醇及催乳素的浓度明显升高，差异有显著性，B组较c组及D组外周血中的雌二醇浓度下降，差异有显著性；A组雌激素、孕激素受体的阳性表达率较B、C、D组升高，差异有显著性。结论 高雌激素水平对脂多糖诱导的急性肺损伤有保护作用，而低雄激素、高催乳素水平可能是对脂多糖诱导的急性肺损伤起辅助性保护性作用。     

Assisted spontaneous breathing during early acute lung injury

In the early phase of their disease process, patients with acute lung injury are often ventilated with strategies that control the tidal volume or airway pressure, while modes employing spontaneous breathing are applied later to wean the patient from the ventilator. Spontaneous breathing modes may integrate intrinsic feedback mechanisms that should help prevent ventilator-induced lung injury, and should improve synchrony between the ventilator and the patient's demand. Airway pressure release ventilation with spontaneous breathing was shown to decrease cyclic collapse/recruitment of dependent, juxtadiaphragmatic lung areas compared with airway pressure release ventilation without spontaneous breathing. Combined with previous data demonstrating improved cardiorespiratory variables, airway pressure release ventilation with spontaneous breathing may turn out to be a less injurious ventilatory strategy.     

Assisted spontaneous breathing during early acute lung injury

In the early phase of their disease process, patients with acute lung injury are often ventilated with strategies that control the tidal volume or airway pressure, while modes employing spontaneous breathing are applied later to wean the patient from the ventilator. Spontaneous breathing modes may integrate intrinsic feedback mechanisms that should help prevent ventilator-induced lung injury, and should improve synchrony between the ventilator and the patient's demand. Airway pressure release ventilation with spontaneous breathing was shown to decrease cyclic collapse/recruitment of dependent, juxtadiaphragmatic lung areas compared with airway pressure release ventilation without spontaneous breathing. Combined with previous data demonstrating improved cardiorespiratory variables, airway pressure release ventilation with spontaneous breathing may turn out to be a less injurious ventilatory strategy.     

Deterioration of previous acute lung injury during neutropenia recovery

DESIGN: Although neutropenia recovery is associated with a high risk of deterioration of respiratory condition, no studies designed to identify risk factors for acute respiratory distress syndrome (ARDS) in this situation have been published. SETTING: Medical ICU in a French teaching hospital. SUBJECTS: We conducted a study to describe critically ill cancer patients with ARDS during neutropenia recovery (defined as the 7-day period centered on the day the neutrophil count rose above 1000/mm3 [day 0]) and to compare them with critically ill cancer patients without ARDS during neutropenia recovery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a 10-yr period, 62 critically ill cancer patients recovered from neutropenia, of whom 21 experienced ARDS during neutropenia recovery, with a median time of -1 days (-2.5-1) between day 0 and ARDS. In-ICU mortality in these 21 patients was 61.9%. As compared with non-ARDS patients, ARDS patients were less likely to have myeloma and more likely to have leukemia/lymphoma treated with adriamycin, a history of pneumonia before neutropenia, and a neutropenia duration >10 days; they had a shorter time since malignancy diagnosis and a longer time from chemotherapy to neutropenia. Neither the leukocyte counts on day 0 nor those during the 6-day neutropenia recovery period were predictive of ARDS. CONCLUSIONS: Patients with acute respiratory failure after prolonged neutropenia complicated by pneumonia are at increased risk for ARDS.     

气道内应用地塞米松对急性肺损伤及急性呼吸窘迫综合征的防治作用

目的 探讨因创伤等引起的急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)患者气道内给予地塞米松的治疗效果。方法 64例符合ALI／ARDS诊断标准的患者，建立人工气道，行机械通气。充分湿化吸痰后，首次气道内注入10mg地塞米松，第1天气道内注入地塞米松5mg／h，第2天注入5mg／2h，第3天注入5mg／4h，3d后逐日减为2．5mg／4h、2．5mg／6h、2．5mg／8h后停药；地塞米松全身用量为10～20mg／d，2～3d后停药。结果 ①呼吸机治疗气道峰值压力平均降低8．20cmH2O；②动脉氧分压升高至61．90～93．00mmHg。结论 气道内应用地塞米松能明显改善呼吸功能，阻止ALI病程向ARDS的发展。同时由于激素局部用药，减少大剂量激素用药不良作用。     

大鼠重症急性胰腺炎时急性肺损伤的实验研究

目的　研究内毒素 (endotoxin ,ET)、细胞因子 (cytokine,CK)、氧自由基 (oxygenfreeradi cals ,OFR)等在重症急性胰腺炎 (severeacutepancreatitis,SAP)时急性肺损伤 (acutelunginjury ,ALI)发病机制中的作用。方法　采用胰管逆行注射 1 5 %去氧胆酸钠制成大鼠重症急性胰腺炎时ALI模型。选用纯雄性健康Wistar大鼠共 4 0只 ,体重 2 2 0～ 2 5 0g,随机分成两组 :假手术对照组 (Sham ,n =10 ) ;SAP模型组(SAP ,n =30 ) ,分别于造模后 2 4h活杀。测定动脉血气 ,血清淀粉酶的含量 ,血清内毒素及血清和肺组织匀浆中的TNF α、IL 6、MDA、SOD的含量 ,肺湿 /干系数以及肺组织病理学改变。结果　SAP组血清内毒素 ,血淀粉酶 ,血清及肺组织匀浆中TNF α、IL 6、OFR均较Sham组明显升高 (P <0 0 1) ;动脉血气显示肺损伤严重 ,肺湿 /干比值较Sham组明显升高 ,肺通透性明显升高 ,肺病理学形态改变加重。结论　ET、TNF、IL 6、OFR在SAP时ALI发生发展中起了重要作用     

Pulmonary capillary pressure during acute lung injury in dogs

OBJECTIVES: To measure pulmonary capillary pressure and pulmonary artery occlusion pressures both during control conditions and during acute lung injury and to evaluate the effects of inotropic therapy and volume loading on these measurements after lung injury. DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eighteen heartworm-free mongrel dogs. INTERVENTIONS: Dogs were anesthetized (sodium pentobarbital, 30 mg/kg intravenously), intubated, and mechanically ventilated. A femoral artery and vein and the right external jugular vein were cannulated. After a median sternotomy, two pulmonary artery catheters were inserted via the jugular vein into the left and right lower lobar pulmonary arteries. Oleic acid (0.03 mL/kg) was administered to all dogs via the left pulmonary artery catheter, whereas the right lower lobe served as control. A baseline group of dogs received no further interventions, whereas two additional groups were given dobutamine (30-60 microg x kg(-1) x min(-1)intravenously) or saline boluses (1-2 L) before measurements were obtained after oleic acid lung injury. MEASUREMENTS AND MAIN RESULTS: Capillary pressure was estimated in both lower lung lobes by using the pulmonary artery occlusion method. Pulmonary capillary and pulmonary artery occlusion pressures were measured before and 2 hrs after oleic acid administration. Left lower lobar capillary pressure increased in all three groups, as did the difference between capillary pressure and pulmonary artery occlusion pressure. Capillary pressure in the control right lower lobe increased significantly only in the saline-loaded dogs, whereas the difference between the right-sided capillary and occlusion pressures increased only in the dogs given dobutamine. CONCLUSIONS: Oleic acid lung injury increases pulmonary capillary pressure independent of pulmonary artery occlusion pressure. The gradient between the two pressures was not significantly affected by volume loading or dobutamine infusion.     

Direct effects of protein S in ameliorating acute lung injury

Summary. Objective: Protein S may exert an anticoagulant activity by enhancing the anticoagulant activity of activated protein C and/or by directly inhibiting the prothrombinase complex. Protein S itself may also directly regulate inflammatory responses and apoptosis. The role of protein S in acute lung injury (ALI) was unknown. This study evaluated the effect of protein S on ALI in the mouse. Methods: Animal ALI was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS). Mice were treated with protein S or saline by intraperitoneal injection 1 h before LPS instillation. Results: Activated protein or protein S alone and combined activated protein C + protein S therapy decreased inflammatory markers and cytokines in mice with acute lung injury. In LPS‐treated mice compared with controls ALI was induced as shown by significantly increased levels of total protein, tumor necrosis factor‐α, interleukin‐6 and monocyte chemoattractant protein‐1 in the bronchoalveolar lavage fluid. Mice with ALI treated with protein S had significantly decreased concentrations of tumor necrosis factor‐α and interleukin‐6 in the lung compared with untreated animals. Thrombin‐antithrombin III, a marker of the activity of the coagulation cascade, was unchanged. Protein S inhibited the expression of cytokines in vitro and increased activation of the Axl tyrosine kinase pathway in A549 epithelial cells. Conclusion: Protein S protects against LPS‐induced ALI, possibly by directly inhibiting the local expression of inflammatory cytokines without affecting coagulation.     

卡托普利对百草枯致急性肺损伤的保护作用

Objective To establish paraquat(PQ)induced acute lung injury models induced by paraquat (PQ), and to study the protective effects of angiotension converting enzyme inhibitors (ACEI) with eaptopril (CAP) on the PQ posioning. Method All experiments were made in the central laboratory of Union Hospital. Human umbilical vein endothelial cells (HUVECs) were incubated with different concentration of paraquat and captopril to establish experimental models. Half of cell survival rate detected with MTF assay to judge whether the model was successful or not. Three groups were divided according to the different drug. application: normal control group without any drug intervetion, PQ group exposed to paraqnat with the concentration of 400 μmol/L and CAP group additionally exposed to captopril with concentration of 10 μmoL/L, which was repartifioned to three groups (CAPA, CAPB and CAPC) according to the different intervention time. The supematant was collected to measure the concentration of malondialdehyde(MDA) and superoxide dismutase(SOD) after PQ injury for 24 hours, cy-tochrome C detected by immunocytochemistry and apoptosis detected by flow cytometry. Data were expressed as mean±standard error of the mean (x±s). Statistical 'analysis was carried out with the soft SPSS 16.0. Results MTr assay detected the concentration & time of PQ intervention and the data of CAP groups, using the single-re-season variance analysis, F value were 56.734,172.025, P < 0.01 respectively, thus to suecessfidly construct the PQ model and determine the concentration of CAP intervention groups. Relative to the PQ group, MDA as well as levels of cytochrome C of the CAP group were significantly decreased (t = 5.913,3.945,-3.426, P <0.01); while SOD were markedly increased (t = 5.463,-2.292,-1.297, P < 0.01). It also showed that captopril markedly decreased PQ induced the rate of HUVECs apoptosis, the percentagen of PQ group apoptosis was 46.1%, while CAP groups apoptnsis were 4.3 %, 9.2% and 17 % respectively. Conclusions Captopril has the ability to scavenge reactive oxygen species, and to protect against the paraquat induced lung toxicity on HUVECs, which pro-vide the infonnafion for basic research and clinical treatment of PQ posioning.     

卡托普利对百草枯致急性肺损伤的保护作用

目的 构建百草枯(paraquat,PQ)诱导的急性肺损伤细胞模型,探讨血管紧张素转化酶抑制剂卡托普利(captopril,CAP)对PQ中毒模型的保护作用.方法实验地点在武汉协和医院中心实验室,采用人脐静脉内皮细胞系(human umbilical vein endothelial cells,HUVECs),给予含不同浓度的PQ和CAP堵养基孵育HUVECs,制备实验模型,MTT法检测细胞活性,半数成活率判定模型成功与否.依据干预药物的不同确定实验分组:不予以药物干预为正常对照组(normal control group,NCG);给予含400μmol/LPQ的培养基制备PQ损伤组;在PQ损伤同时予以CAP(10μmol/L)干预的为CAP保护组;因CAP干预时间的不同,分CAPA,CAPB,CAPC.检测在PQ损伤24 h后检测培养幕上清内SOD、MDA;免疫组织化学染色法检测业细胞结构的变化;流式细胞仪检测细胞凋亡,数据采用(x±s)表示,应用SPSS 16.0软件行统计学分析.结果 MTT法榆测PQ作用浓度,时间和CAP各组数值,采用单因素方差分析,F值分别为56.734,172.025,P<0.01,成功构建了PQ模型及确定CAP干预浓度;与PQ组相比,CAP各组MDA含量降低(t分别为5.913,3.945,-3.426,P<0.01),而SOD含量升高(t分别为5.463,-2.292,-1.297,P<0.01);细胞色素C含量明显减少及CAP绀凋亡率降低.结论 血管紧张素抑制剂CAP具有清除活性氧自由基作用,可拮抗PQ对HUVECs细胞的损伤作用,为PQ中毒的基础研究和临床治疗提供思考.     

美洛昔康对兔急性肺损伤保护作用的研究

目的观察内毒素致兔急性肺损伤（ALI）时肺组织血栓素B2（TXB2）／6-酮-前列腺素F1α（6-keto—PGF1α）和内皮素-1（ET-1）变化及美洛昔康的影响，探讨美洛昔康对急性肺损伤干预的机制。方法将24只日本大耳白兔随机分为对照组（A组）、致伤组（B组）、美洛昔康干预组（C组）。各组分别于0、0．5、2、4h观测动脉血气、呼吸变化，4h处死动物，用放射免疫分析方法检测肺组织TXB2、6-keto—PGF，d、ET-1含量，行肺组织病理学观察并评分。结果静注内毒素后，B组动物呼吸显著加快，氧舍指数下降，肺组织TXB2／6-keto—PGF1α、ET-1均高于A组（P〈0．01），病理检查见肺水肿、出血等病理改变，病理评分也显著高于A组。C组呼吸稍增加，氧合指数稍降，肺组织TXB2／6-keto—PGF1α、ET-1、病理评分均低于B组（P〈0．01）。结论美洛昔康可通过降低肺中TXB2／6-keto—PGF1α比值和ET-1的含量，在一定程度上减轻内毒素对肺的损伤作用。     

二氧化硫对脓毒症大鼠致肺损伤炎性介质的调节

目的 探索内源性二氧化硫(sulfur dioxide,SO2)对脓毒症大鼠所致急性肺损伤过程炎性介质的调节作用.方法 雄性Sprague Dawley大鼠24只随机(随机数字法)被分入假手术对照组(control组),假手术+SO2组(SO2组),脓毒症组(sepsis组),脓毒症+SO2组(sepsis+ SO2组),每组6只.通过肺组织损伤半定量评分(Index of quantitative assessment,IQA)及肺组织湿干质量比(wet/dry weight ratio,W/D)对肺损伤进行评价.检测血浆SO2、白细胞介素6、8及10(interleukins-6,IL 6、interleukins-8,IL 8、interleukins-10,IL 10)及单核细胞趋化蛋白-1(Monocytechemotactic protein-1,MCP-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)含量.结果 脓毒症大鼠IQA及W/D与对照组相比显著升高(P均＜0.01),给予SO2干预后显著降低(P均＜0.01).血浆SO2含量在脓毒症组(3.17 ±3.44)μmol/L与对照组(5.87 ±1.96)μmol/L下降,给予SO2干预后显著升高(9.78±3.26) μmol/L,P＜0.01;血浆IL 6、IL 8、IL 10及MCP-1、TNF-α含量在脓毒症组分别为(87.08 ±22.03)、(79.82±19.69)、(66.38 ±21.77)、(157.58 ±42.36)及(65.04±19.42) pg/mg,对照组分别为(47.41 ±9.64)、(42.25±8.16)、(31.96±4.63)、(67.65±10.18)及(33.83 ±5.75)相比显著升高(P均＜0.01);给予SO2干预后分别为(66.01±16.52)、(61.52±18.32)、(45.61 ±16.47)、(117.86 ±34.20)及(61.49±15.33) pg/mg降低(IL 6及IL 8,P均＜0.05,IL 10及MCP-1,P均＜0.01).结论 在脓毒症所致肺损伤的发病过程中,内源性SO2可以通过抑制MCP-1、TNF-α进而减轻炎症因子的表达起到保护作用.     

Pulmonary dysfunction during paraquat-induced lung injury: a model of acute alveolar injury

Acute lung injury produced by paraquat causes progressive pulmonary insufficiency. To define the pattern of this injury, the sequence of changes in respiratory mechanics and pulmonary gas exchange was studied in eight mongrel dogs which received repetitive doses of paraquat intraperitoneally. Four other dogs served as controls. All dogs were studied while supine during halothane anesthesia. After baseline measurements, saline (control) or paraquat was administered and the studies repeated at 2, 4, 7, and 9 days. Control dogs showed no significant changes. Dogs receiving paraquat had reduced lung volume, decreased lung compliance with a shift of the static deflation pressure-volume curve downward and to the right, and hypoxemia which could not be entirely accounted for by an increased right-to-left intrapulmonary shunt. This study demonstrated that repeated doses of paraquat given intraperitoneally produced a pattern of acute lung injury in the dog which permitted the study of respiratory mechanics and gas exchange during progressive stages of lung injury.     

Systemic oxygen delivery and consumption during acute lung injury in dogs

When oxygen delivery (QO₂ = Qt × CaO₂) is reduced in healthy animals, oxygen uptake by tissues (VO₂) is maintained by an increase in the O₂ extraction ratio ((CaO₂ − CvO₂)/CaO₂) until a critical level of delivery QO₂C is reached, below which VO₂ becomes dependent on QO₂. In patients with adult respiratory distress syndrome (ARDS), VO₂ becomes dependent on O₂ delivery even at high levels of QO₂ implying a systemic O₂ extraction defect. To determine whether lung injury, or its management with positive end-expiratory pressure (PEEP) and high inspired oxygen fractions (F1O₂), might disrupt O₂ extraction by peripheral tissues, we compared the critical O₂ delivery and extraction ratio in 30 anesthetized and paralyzed dogs in four groups. One group (n = 7) received oleic acid to produce an acute lung injury (F_lO₂ = 1.0) and a second group (n = 7) was maintained with PEEP (F_lO₂ = 1.0) after receiving oleic acid. A third group (n = 8) received no oleic acid (F_lO₂ = 1.0), and a fourth group received no oleic acid and was ventilated with room air. The critical O₂ delivery was determined in each animal as QO₂ was lowered in a stepwise manner by controlled blood removal. Neither the critical QO₂ nor critical O₂ extraction ratios were different (P> .05) among oleic acid, PEEP-treated, or hyperoxic control animals. Similarly, the critical QO₂ determined from the point at which arterial lactate began to increase showed no difference among groups. Thus, neither acute lung injury produced with oleic acid nor its treatment with PEEP was associated with a peripheral O₂ extraction defect. However, a linear regression across all groups demonstrated a positive correlation between the arterial PO₂ and corresponding critical O₂ delivery (r = < P < .05). These results suggest that high arterial O₂ tensions may contribute to an impairment of peripheral O₂ extraction.     

Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is an uncommon complication of allogeneic blood transfusion manifested typically by shortness of breath, fever, and hypotension. It has been estimated to occur in 0.04% to 0.16% per patient transfused. TRALI has been identified as an important cause of transfusion-related morbidity and mortality. Despite the increasing recognition that TRALI represents an important clinical syndrome, much about the pathogenesis, treatment, and prevention of TRALI is poorly understood or is controversial. In this report, what is known about TRALI is summarized and some of the areas in which knowledge and/or consensus are currently lacking are identified.     

Transfusion-related acute lung injury

Noncardiogenic pulmonary edema after transfusion therapy is an infrequent but hazardous complication. The occurrence of this entity is linked to the presence of circulating leukoagglutinins. The clinical features are described on the basis of four cases. The hemodynamic changes, underlying mechanisms and therapeutic strategies are discussed.