小儿ALI/ARDS临床研究

急性肺损伤(ALI)是心源性以外的各种肺内、外致病因素所引起的急性炎症反应,表现为急性、进行性低氧性呼吸衰竭,最终严重阶段为急性呼吸窘迫综合征(ARDS),小儿急性呼吸窘迫综合征是儿科重症监护室(PICU)中病死率极高的危重病之一,我科于2004年至2005年参加全国小儿急性呼吸窘迫综合征协作组对小儿ALI/ARDS的流行病学进行研究,同时开展小儿ALI/ARDS机械通气下呼吸力学研究.     

低分子肝素雾化吸入治疗ALI/ARDS的临床疗效观察

目的探讨雾化吸入低分子肝素治疗急性肺损伤的临床疗效及可能的作用机制。方法选择42例急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的患者,随机分为对照组、皮下组和雾化组,对照组使用常规治疗,皮下组和雾化组则分别在常规治疗基础上采用皮下注射及气道雾化吸入低分子肝素钠。观察和比较三组患者治疗7 d后氧合指数、急性生理学与慢性健康状况Ⅱ(APACHEⅡ)评分I、L-6以及PLT、APTT变化、7 d死亡率。结果各组治疗7 d后各项指标较前有好转,抗凝组(皮下组和雾化组)较对照组氧合指数明显升高I,L-6、APACHEⅡ评分下降更显著。其中,雾化组氧合指数优于皮下组,而IL-6、A-PACHEⅡ评分较皮下组高(P<0.05)。抗凝组治疗后PLT、APTT与对照组比较无差异。皮下组、雾化组、对照组死亡率分别为6.7%,11.1%4,4.4%,组间比较有差异,抗凝组优于对照组。结论雾化吸入低分子肝素治疗ALI/ARDS,能够改善氧合;可能通过抑制IL-6等炎症介质的释放,降低全身炎症反应,从而降低患者的死亡率。     

两种机械通气联合肺表面活性物质用于ALI/ARDS新生儿治疗效果对比研究

目的 对比两种不同机械通气方式(常频机械通气、高频振荡机械通气)联合肺表面活性物质用于急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)新生儿治疗的效果及对炎性因子的影响.方法 收集郑州大学附属儿童医院在2019...     

Role of surfactant in the paradigm of ALI／ARDS

ALI/ARDS is a devastating complication occurring in critically ill patients, and despite extensive research ettects over the last 30 years, current mortality remains unacceptably high at approxjmately 30% to 40%. Although several different insults can ultimately lead to ALI/ARDS, the clinical definition of this syndrome is relatively simple, and involves commmon physiologic criteria. Indeed, it was these criteria(hypoxemia and decreased lung compliance without heart failure) together with the pathologic similarities to infants with     

Rab26对TLR4介导的ARDS的作用及机制研究

目的 探讨Rab26对TLR4所介导的急性呼吸窘迫综合征的作用及机制研究。方法 实验选用健康野生级C57小鼠及敲除基因鼠（Rab26-/-）,构建对照组（正常野生型C57小鼠+气管内滴注5 mg/kgLPS,n=10）、实验组（敲除基因鼠+气管内滴注5 mg/kg LPS,n=10）,观察6 h后各小组小鼠经腹主动脉取动脉血进行血气分析并处死小鼠;酶联免疫吸附法检测血清炎性因子TNF-α、IL-6;留取小鼠肺组织称重计算肺干湿比（W/D比值）;肺组织HE染色后做病理切片观察各组小鼠肺组织病理变化,并对肺损伤组织进行评分。结果 在构建肺损伤模型后6 h,与对照组相比,实验组小鼠氧合指数、血清炎性因子TNF-α、IL-6水平明显下降(P<0.01);实验组小鼠肺组织的W/D值明显更高（P<0.01）;病理切片结果 显示,实验组小鼠肺组织破坏更重,肺泡壁充血水肿、肺泡萎陷不张更为显著,肺损伤评分明显高于对照组(P<0.01)。结论 Rab26对TLR4所介导的ARDS炎性因子表达,以及激活下游信号通路有抑制作用,为将来急性肺损伤诊治的方向和重点进一步提供了研究依据。     

ALI／ARDS思者侧卧位通气的临床观察和护理特点

目的 初步观察侧卧位通气治疗ALI／ARDS的临床效果，并探讨其治疗机理及护理特点。方法 对13例ALI／ARDS患者施行侧卧位通气，有效者持续1h，做血气分析；然后恢复仰卧位，1h后再做血气分析。两次测量值与侧卧位前的血气分析值进行比较。结果 8例有效者侧卧位通气1h后Sp02、Pa02、Pa02／Fi02升高，与侧卧位前比较有显著性差异，P＜0．01；恢复仰卧位1h后下降，但仍高于侧卧位前，P＞0．05 结论 侧卧位通气对部分ALI／ARDS患者有治疗作用，与俯卧位通气相比，实施更容易，值得临床进一步探讨。     

床旁肺超声联合TNF-α、pro-BNP用于鉴别ALI/ARDS和ACPE的应用价值研究

目的 探究床旁肺超声联合TNF-α、pro-BNP用于鉴别急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)和急性心源性肺水肿(ACPE)的应用价值。方法 选取我院ICU临床诊断为ALI/ARDS、ACPE患者,各50例,采用床旁肺超声联合B型利钠肽前体(pro-BNP)、肿瘤坏死因子α(TNF-α)检测,探究其在ALI/ARDS和ACPE中的鉴别价值。结果 ALI/ARDS患者TNF-α、pro-BNP指标均显著高于ACPE患者(P<0.05),ALI/ARDS患者各肺区肺通气评分均高于ACPE患者(P<0.05)。结论 ALI/ARDS和ACPE患者的TNF-α、pro-BNP指标存在显著差异,结合床旁肺超声检查,利用各肺区肺通气评分可进一步提升诊断效果,值得应用。     

抗氧化剂对ALI大鼠细胞因子的影响效应探讨

目的 探讨ALI时细胞因子的变化及抗氧化剂对ALI细胞因子的影响效应。方法 健康、成熟Wister大鼠60只随机分为2组,模型（对照）组和治疗（实验）组每组各30只,均以大肠杆菌腹腔注射,以氧合指数、肺湿/干重比、肺组织病理改变为标准,建立ALI动物模型。治疗（实验）组在注射大肠杆菌30min后,经大鼠尾静脉注射抗氧化剂——还原型谷胱甘肽。分别于注射大肠杆菌后3h,6h,12h测定血中IL-8、IL-10的变化。结果 模型（对照）组注射大肠杆菌后3h出现ALI症状,6h更为明显,12h口吐粉红色分泌物,解剖后肉眼所见双肺有明显水肿,出血点。氧合指数及W/D均达到ALI诊断标准。治疗（实验）组3h无明显变化,6h部分大鼠呼吸稍促,12h肺组织仅轻度水肿。治疗（实验）组肺湿/干比在3h、6h、12h检测值均低于模型（对照）组,6h、12h时差异存在统计学意义（p﹤0.05）。治疗（实验）组大鼠在使用还原型谷胱甘肽后,3h、6h、12h测得IL-8检测值（单位PG/ml）低于模型（对照）组,各时段差异均存在统计学意义（p﹤0.05）。治疗（实验）组大鼠在使用还原型谷胱甘肽后,3h、6h、12h测得IL-10检测值（单位PG/ml）高于模型（对照）组,6h、12h时差异均存在统计学意义（p﹤0.05）。结论 ALI时存在炎性介质的失控与失衡,应用抗氧化剂——还原型谷胱甘肽后可有效调控炎性介质,有助于减少超氧化物和溶酶体的释放、减轻炎性反应,从而降低ALI的发生几率。     

脓毒症导致ALI/ARDS患者外周血TLR4及血清TNF-α、SP-A的变化及相关性分析

目的探讨脓毒症导致ALI/ARDS患者外周血TLR4及血清TNF-α、SP-A的表达及相关性分析。方法 20例脓毒症导致ALI/ARDS患者的外周血在治疗前和治疗后被收集。单核细胞分离后检测TLR4 mRNA水平,ELISA方法检测血清TNF-α和SP-A水平。结果16例治愈的脓毒症导致ALI/ARDS患者治疗后TNF-α和SP-A水平显著低于治疗前。单核细胞TLR4 mRNA水平、血清TNF-α和SP-A水平相互之间pearson相关分析显示正相关。结论脓毒症导致ALI/ARDS患者单核细胞TLR4 mRNA水平、血清TNF-α和SP-A水平和病情的急性炎性反应呈正相关。     

红景天苷对急性肺损伤/急性呼吸窘迫综合征大鼠的保护作用

摘 要 目的：探讨红景天苷注射液对急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）大鼠的保护作用。方法: 50只大鼠随机分为5组：正常对照组,模型对照组,红景天苷高、中、低（8.0,4.0,2.0 mg·kg^-1 ）剂量组,每组10只。采用油酸0.1 ml·kg^-1 经尾静脉注射制备ALI/ARDS模型。腹腔注射给药,qd,连续给药3 d。模型制备成功后24 h经颈动脉采集血样1.0 ml行血气分析。给药第3天检测肺湿干质量比、动脉氧分压、HE染色肺组织病理,并采用ELISE法检测大鼠血液中高迁移率族蛋白 1（HMGB1）和角蛋白 14（KRT 14）的表达。结果:红景天苷各剂量组的HMGB1和KRT 14表达均低于模型对照组,中、高剂量组与模型对照组相比差异有统计学意义（P<0.05）;红景天苷的剂量与药效呈正相关,中、高剂量组与低剂量相比差异有统计学意义（P<0.05）。红景天苷各剂量组的动脉氧分压高于模型对照组,肺湿干质量比低于模型对照组,中、高剂量组与模型对照组相比差异有统计学意义（P<0.05）;红景天苷的剂量与药效呈正相关,中、高剂量组与低剂量相比差异有统计学意义（P<0.05）。红景天苷各剂量组的肺组织病理与模型对照组相比有所改善。结论:红景天苷能减轻ALI/ARDS大鼠血液中炎症因子HMGB1和KRT 14的表达,减轻肺水肿,提高氧分压,对ALI/ARDS大鼠具有明显的治疗作用。     

严重胸外伤致急性呼吸窘迫综合征的诊治

目的探讨严重胸外伤致急性呼吸窘迫综合征的诊断和治疗。方法对89例严重胸外伤并发急性呼吸窘迫综合征（ARDS）患者的诊断、治疗进行分析与总结。结果全组89例,死亡22例,死亡率为25%,主要死亡原因是多器官功能衰竭（MSOF）。结论早期诊断,保持呼吸道通畅,正确使用呼吸机治疗,及时处理休克和多发伤等综合治疗,是降低本病死亡率的有效方法。     

无创-有创序贯性机械通气治疗急性呼吸窘迫综合征的疗效

目的 探讨无创-有创序贯性机械通气(MV)治疗急性呼吸窘迫综合征(ARDS)的应用价值.方法 62例需MV的ARDS患者采取随机分为两组,每组31例.A组行气管插管有创MV;B组先给予无创MV,一旦无创通气失败则改气管插管行无创一有创序贯性机械通气.MV前后氧合指数(OI)、呼吸频率(RR)、心率(HR)以及呼吸机相关性肺炎(VAP)发生率、总MV时间、住重症监护病房(ICU)时间、病死率等方面进行比较.结果 与治疗前比较,两组治疗3 h后的OI、RR均有显著改善;B组VAP发生率、总MV时间及住ICU时间显著低于A组(P<0.05).结论 无创一有创序贯性机械通气较有创机械通气能降低VAP发生率、缩短MV时间及住ICU时间.     

The complex lipid,SPPCT-800, reduces lung damage,improves pulmonary function and decreases pro-inflammatory cytokines in the murine LPS-induced acute respiratory distress syndrome (ARDS) model

ContextAcute respiratory distress syndrome (ARDS) is a highly fatal, inflammatory condition of lungs with multiple causes. There is no adequate treatment.ObjectiveUsing the murine LPS-induced ARDS model, we investigate SPPCT-800 (a complex lipid) as treatment for ARDS.Materials and methodsC57B16/N mice received 50 μg of Escherichia coli O111:B4 lipopolysaccharide (LPS). SPPCT-800 was given as either: (1) 20 or 200 mg/kg dose 3 h after LPS; (2) 200 mg/kg (prophylactically) 30 min before LPS; or (3) eight 200 mg/kg treatments over 72 h. Controls received saline installations.ResultsAt 48 and 72 h, SpO₂ was 94% and 90% in controls compared to 97% and 94% in treated animals. Expiration times, at 24 and 48 h, were 160 and 137 msec for controls, but 139 and 107 msec with SPPCT-800. In BALF (24 h), cell counts were 4.7 × 10⁶ (controls) and 2.9 × 10⁶ (treated); protein levels were 1.5 mg (controls) and 0.4 mg (treated); and IL-6 was 942 ± 194 pg/mL (controls) versus 850 ± 212 pg/mL (treated) [at 72 h, 4664 ± 2591 pg/mL (controls) versus 276 ± 151 pg/mL (treated)]. Weight losses, at 48 and 72 h, were 20% and 18% (controls), but 14% and 8% (treated). Lung injury scores, at 24 and 72 h, were 1.4 and 3.0 (controls) and 0.3 and 2.2 (treated).Discussion and conclusionsSPPCT-800 was effective in reducing manifestations of ARDS. SPPCT-800 should be further investigated as therapy for ARDS, especially in longer duration or higher cumulative dose studies.     

化学吸入性急性肺损伤/急性呼吸窘迫综合征患者的药学监护实践

摘 要 目的： 探讨临床药师对化学吸入性急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）患者的药学监护模式,保障患者用药安全、合理和有效。方法: 根据化学吸入性ALI/ARDS患者的药物治疗特点,对患者进行药学监护,有针对性提出用药建议。结果: 通过药学监护,可提高化学吸入性ALI/ARDS患者用药的安全性、合理性及有效性,减少药品不良反应的发生。结论:临床药师积极开展药学服务,协同临床医师优化给药方案,有利于患者用药安全、有效。     

甘氨酸对油酸致小鼠急性肺损伤的保护作用

目的 探讨甘氨酸对油酸致小鼠急性肺损伤的保护作用．方法 健康昆明小鼠随机分为急性肺损伤(ALI)组、甘氨酸(Gly)组和对照组。1h后测定各组动物血气分析,肺系数,血浆IL-10浓度和光镜观察肺病理改变。结果 甘氨酸可显著抑制油酸致小鼠急性肺损伤时的肺系数增加,升高动脉血氧分压和血浆IL-10浓度,明显减轻肺组织学病变。结论 甘氨酸对油酸引起的急性肺损伤有防治作用。     

Protective and predictive role of Mucin1 in sepsis-induced ALI/ARDS

ObjectiveWe aimed to investigate whether inhibition of MUC1 would aggravate sepsis-induced ALI, and explore the predictive value of plasma MUC1 for sepsis patients with or without ARDS.Materials and methodsMUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. Expression levels of MUC1, TLR 4 and HIF-1α were detected by Western blot. In addition, plasma MUC1 levels of enrolled patients were detected by ELISA on the day of admission and on the 3rd day. ROC curve was used to determine the predictive value of MUC1 in sepsis patients with ARDS.ResultsOur results showed that inhibition of MUC1 could aggravate sepsis-induced acute lung injury and increase the expression of inflammatory cytokines in sera and BALF of sepsis mice. At the same time, we confirmed that inhibition of MUC1 could significantly decrease HIF-1α expression and thereby activate the expression level of TLR4. HIF-1α was a negative regulator of TLR-4. In addition, plasma MUC1 levels of sepsis patients with ARDS were significantly higher than those without ARDS and healthy adults. ROC curve showed that predictive value of plasma MUC1 on sepsis with ARDS on the 3rd day of enrollment was higher than the day of enrollment.ConclusionMUC1 could inhibit the expression of TLR-4 by stabilizing HIF-1α, thereby alleviate sepsis-induced lung injury and protect organ function. At the same time, elevated MUC1 levels in plasma had a good predictive valud on whether patients with sepsis would develop ARDS.     

Endothelial pathomechanisms in acute lung injury

Acute lung injury (ALI) and its most severe extreme the acute respiratory distress syndrome (ARDS) refer to increased-permeability pulmonary edema caused by a variety of pulmonary or systemic insults. ALI and in particular ARDS, are usually accompanied by refractory hypoxemia and the need for mechanical ventilation. In most cases, an exaggerated inflammatory and pro-thrombotic reaction to an initial stimulus, such as systemic infection, elicits disruption of the alveolo-capillary membrane and vascular fluid leak. The pulmonary endothelium is a major metabolic organ promoting adequate pulmonary and systemic vascular homeostasis, and a main target of circulating cells and humoral mediators under injury; pulmonary endothelium is therefore critically involved in the pathogenesis of ALI. In this review we will discuss mechanisms of pulmonary endothelial dysfunction and edema generation in the lung with special emphasis on the interplay between the endothelium, the immune and hemostatic systems, and highlight how these principles apply in the context of defined disorders and specific insults implicated in ALI pathogenesis.     

辛伐他汀对脓毒症小鼠肺损伤的保护作用

目的观察辛伐他丁对脓毒症小鼠急性肺损伤的保护作用,并探讨其可能机制。方法采用盲肠结扎穿孔术制备脓毒症小鼠模型,将72只雄性C57BL/6小鼠随机分成3组:假手术组、脓毒症急性肺损伤组(脓毒症组)、脓毒症+辛伐他汀治疗组(治疗组)。治疗组给予辛伐他汀0.2μg/g,q12h腹腔注射1周;假手术组、脓毒症组给予等量安慰剂腹腔注射1周。分别于造模后6、12、24 h留取肺脏标本。HE染色观察肺组织病理学变化,免疫组化检测肺组织toll样受体4(Toll-like receptor 4,TLR4)蛋白的表达,ELISA测定肺组织匀浆中IL-1β及TNF-α的表达水平。结果与假手术组比较,造模后6、12、24 h,脓毒症组肺组织病理学评分、肺组织TLR4蛋白的表达,以及TNF-α、IL-1β水平明显升高(P<0.05);与脓毒症组相比,治疗组上述指标明显降低(P<0.05)。结论辛伐他汀通过抑制TLR4信号转导通路,减少其下游炎症介质TNF-α、IL-1β的释放,对脓毒症导致的急性肺损伤具有一定保护作用。     

高碳酸血症对兔急性呼吸窘迫综合征保护作用的实验研究

目的通过测定血浆及支气管肺泡灌洗液（BALF）IL-8浓度等参数探讨高碳酸血症对兔急性呼吸窘迫综合征的保护作用。方法通过油酸静脉注射建立兔急性呼吸窘迫综合征动物模型并行气管切开连接小型动物呼吸机（呼吸模式为AC模式,潮气量为8 mL/kg;呼吸频率为51次/min;PEEP为5 cm H2O;吸入氧浓度FiO2为0.60）。将造模成功兔随机分为两组,实验组给予外源性CO2吸入,吸入浓度（FiCO2）为0.06,实验对照组不给予外源性CO2吸入。分别观察试验组与实验对照组兔于造模成功后180 min血浆及支气管肺泡灌洗液（BALF）中白细胞介素-8（IL-8）水平。结果试验组兔于造模成功后180 min血浆及支气管肺泡灌洗液（BALF）中白细胞介素-8（IL-8）水平明显低于对照组。结论高碳酸血症能够降低兔急性呼吸窘迫综合征肺局部和血液IL-8水平,进而减轻肺局部和全身炎症损伤,对兔急性呼吸窘迫综合征产生保护作用。