甘草酸二铵对急性肺损伤大鼠肺组织转化生长因子β1及高迁移率族蛋白1表达的影响

目的 观察甘草酸二铵(GL)对急性肺损伤(ALI)大鼠肺组织转化生长因子β1(TGF-β1)、高迁移率族蛋白1(HMGB1)表达的调控作用及对血清肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)表达的影响.方法 将24只雄性SD大鼠采用随机数字表法分为生理盐水组、ALI组和GL干预组,每组8只.ALI组、GL干预组分别给予内毒素(LPS)5 mg/kg尾静脉注射;LPS注射前1 h,GL干预组给予GL 20 mg/kg静脉注射.观察12 h后各组大鼠肺组织病理,测定肺湿干质量比(W/D)、PaO2,并采用逆转录-PCR反应检测肺组织TGF-β1 mRNA、HMGB1 mRNA的表达,ELISA法测定血清TNF-α、IL-10浓度.结果 ①ALI组TNF-α明显高于生理盐水组(P<0.01)和GL干预组(P<0.01).ALI组IL-10明显高于生理盐水组(P<0.01),但低于GL干预组水平(P<0.05).②ALI组TGF-β1 mRNA、HMGB1 mRNA的表达水平明显高于生理盐水组 (P均<0.01)和GL干预组(P<0.05和P<0.01).③ALI组肺组织出现充血、水肿、中性粒细胞浸润,GL干预组肺部炎症较ALI组减轻.结论 甘草酸二铵可能通过抑制TGF-β1 mRNA、HMGB1 mRNA及TNF-α的表达和增强抗炎介质IL-10的表达,从而起到减轻ALI的作用.     

白细胞介素-10对内毒素诱导急性肺损伤大鼠炎症因子的影响

目的研究白细胞介素-10(IL-10)对内毒素诱导急性肺损伤(ALI)大鼠肺组织炎症因子mRNA表达的影响,探讨IL-10对急性肺损伤的保护作用。方法24只SD大鼠随机分为3组:对照组,实验组,治疗组。实验组于尾静脉注射内毒素,治疗组注射内毒素和IL10,对照组注射生理盐水。测定各组肺组织肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)mRNA表达和血浆TNF-α、IL-1β和IL-6水平,观察各组大鼠肺组织的病理改变。结果TNF-α、IL-1β和IL6mRNA的表达:实验组、治疗组高于对照组,P<0.01;实验组高于治疗组,P<0.05。血浆TNF-α、IL1-β、IL-6:实验组高于治疗组对照组,P<0.05。肺组织病理改变:治疗组明显轻于实验组。结论IL10能抑制内毒素诱导ALI大鼠肺组织中TNF-α、IL-1β和IL6mRNA的表达,降低血浆炎症因子水平,减轻肺组织的病理损害,能起到治疗ALI的作用。     

丙酮酸乙酯对内毒素性急性肺损伤大鼠肺组织巨噬细胞炎症蛋白-2表达的影响

目的 观察丙酮酸乙酯(EP)预先给药对内毒素性急性肺损伤(ALI)大鼠肺组织巨噬细胞炎症蛋白-2表达的影响,探讨丙酮酸乙酯可能的保护机制.方法 静脉注射脂多糖(LPS)5 mg/kg,复制大鼠ALI模型.雄性SD大鼠30只随机分为三组:A组为对照组,B组为LPS组,C组为EP+LPS组,于静脉注射LPS前1 h腹腔内注射EP(40 mg/kg).所有动物于注射LPS或生理盐水后6 h颈动脉放血处死,RT-PCR法测定肺组织巨噬细胞炎症蛋白-2 mRNA的表达;酶联免疫吸附法测定肺组织TNF-α和IL-1B的含量.结果 与A组相比,B组、C组肺组织巨噬细胞炎症蛋白-2 mRNA表达增加,肺组织TNF-α和IL-1B含量上升(P<0.05);与B组相比,C组肺组织巨噬细胞炎症蛋白-2 mRNA表达降低,肺组织TNF-α和IL-1B含量降低(P<0.05).结论 丙酮酸乙酯通过下调大鼠LPS诱导的肺组织巨噬细胞炎症蛋白-2表达,降低了TNF-α和IL-1B的释放,减轻ALI大鼠肺部的炎症反应.     

甘草酸二铵对急性肺损伤大鼠肺组织糖皮质激素受体及核因子κB表达的影响

目的 观察甘草酸二铵(GL)对急性肺损伤(ALI)大鼠肺组织核因子κB(NF-κB)、糖皮质激素受体(GR)表达的调控作用及对血清肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)表达的影响.方法 将24只雄性SD大鼠采用随机数字表法分为生理盐水对照组、ALI模型组和GL干预组,每组8只.ALI模型组、GL干预组分别给予内毒素(LPS)5 mg/kg尾静脉注射;IPS注射前1 h,GL干预组给予GL 20 mg/kg静脉注射.观察4 h后各组大鼠肺组织病理,测定肺湿干比(W/D)、PaO_2,并采用逆转录-PCR反应检测肺组织NF-κB mRNA,GR mRNA的表达,western blot法测定肺组织Nf-κB及GR蛋白的表达,ELISA法测定血清TNF-α,IL-10质量浓度.采用SPSS 13.0软件进行统计学分析,各组间均数比较采用单因素方差分析,均数两两比较采用q检验.结果 (1)ALI模型组TNF-α为(153.68±20.42)ng/L,明显高于生理盐水组(43.96±7.57)ng/L(P<0.01)和GL干预组(87.23±7.52)ng/L(P<0.01).ALI模型组IL-10为(42.48±6.81)ug/L,明显高于生理盐水组(24.72±8.03)ng/L(P<0.01),但低于GL干预组水平(58.33±9.62)ug/L(P<0.05).(2)ALI模型组NF-κBmRNA和蛋白的表达水平[分别为(3.414±0.521),(254.7±16.4)]明显高于生理盐水组[分别为(0.432±0.085),(45.6±7.3)](P<0.01),而GRmRNA和蛋白的表达[分别为(0.152±0.025),(11.5±2.3)]则明显低于生理盐水组[分别为(0.434±0.013),(54.6±6.5)](P<0.01);GL干预组NF-κB mRNA和蛋白的表达水平[分别为(1.894±0.272),(133.5±11.7)]明显低于ALI模型组(P<0.01),GR mRNA和蛋白的表达[分别为(0.308±0.033),(28.2±5.6)]则明显高于ALI模型组(P<0.05,P<0.01).(3)ALI模型组肺组织出现充血、水肿、中性粒细胞浸润,GL干预组肺部炎症较ALI模型组减轻.结论 甘草酸二铵可能通过下调NF-κB的表达,同时提高GR的表达,进而调节炎症因子TNF-α及抗炎介质IL-10的表达,从而起到减轻ALI的作用.     

红花注射液对急性肝损伤大鼠炎症因子的影响

目的 探讨红花注射液治疗内毒素性急性肝损伤(ALI)大鼠的作用机制.方法 将80只SD大鼠随机分为对照组(n=8)、ALI组(n=24)、红花干预组(n=24)、还原型谷胱甘肽(TAD)组(n=24).以小剂量脂多糖/D-氨基半乳糖(LPS/D-GalN)制备大鼠ALI模型,使用红花注射液进行干预,并设TAD注射液为阳性对照组.分别于术后6、24和48 h取血和肝组织,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平变化;观察肝组织病理学变化和高迁移率族蛋白B1(HMGB1)的表达水平.结果 ALI组血清ALT、AST、TNF-α、IL-1β水平均明显高于对照组,且肝组织损伤程度及HMGB1表达也明显高于对照组(P均<0.01).红花干预组和TAD组各时间点血清ALT、AST、TNF-α和IL-1β水平明显低于ALI组(P<0.05或P<0.01);肝组织病理损伤程度和HMGB1表达水平也明显低于ALI组(P均<0.01).结论 红花注射液能够有效抑制内毒素性ALI大鼠炎症因子水平,减轻肝组织炎症反应和水肿、坏死程度,对ALI有较好的防治作用.     

亚低温对ARDS大鼠肺部炎症反应影响的研究

目的 探讨亚低温对大鼠内毒素性急性呼吸窘迫综合征(ARDS)肺部炎症反应的影响.方法 大鼠腹腔注射内毒素(LPS,1 mg/kg),16 h后再气管内滴注LPS(3 mg/kg)建立ARDS模型.72只雄性SD大鼠随机分为3组:对照组(C组)、ARDS组(A组)、亚低温组(M组),分别于ARDS时及ARDS后2、4、6 h处死动物,观察肺组织病理形态;计算肺湿质量/干质量(W/D)比值;检测肺组织中TNF-α、IL-8、IL-1β、IL-6含量.结果 3组动物肺组织病理形态有明显的不同.肺W/D:A组、M组均明显高于C组(P<0.01),M组较A组明显降低(P<0.01).肺组织TNF-α、IL-8、IL-1β、IL-6含量:A组、M组明显高于C组(P<0.01),M组明显低于A组(P<0.01).结论 亚低温治疗可减轻内毒素性ARDS大鼠肺部炎症反应.     

内毒素致伤大鼠肺组织促炎与抗炎细胞因子mRNA表达的时相性研究

目的 研究不同剂量内毒素致伤大鼠肺组织促炎和抗炎细胞因子mRNA表达的时相性,并探讨这些细胞因子在全身炎症反应失控和急性肺损伤中的可能作用。方法 采用逆转录-聚合酶链反应(RT-PCR)检测不同剂量脂多糖(LPS)致伤大鼠肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-4、IL-10和IL-13的mRNA表达。结果 随着LPS剂量增加,TNF-α、IL-1β、IL-6、IL-4、IL-10和IL-13的mRNA表达均增强(与生理盐水对照组比较,P均<0.01);LPS≥6 mg/kg组上述细胞因子表达显著高于此剂量以下组(P均<0.01)。表达峰值时间:TNF-α为1 h,IL-6为4 h,其他均在2 h。结论 内毒素致急性肺损伤中,TNF-α是早期表达的促炎细胞因子,而IL-6在炎症进一步发展中发挥作用;抗炎细胞因子IL-4、IL-10、IL-13高表达亦可能促进炎症的放大而不是起保护作用。     

大黄对急性肺损伤大鼠血浆和支气管肺泡灌洗液中炎症细胞因子表达的影响

目的:探讨大黄对实验性急性肺损伤(ALI)大鼠炎症细胞因子在血浆和肺泡灌洗液中表达的影响.方法:用舌下静脉注射内毒素(LPS)的方法复制ALI模型,将145只雄性Wistar大鼠随机分成LPS组、对照组、大黄治疗组和地塞米松治疗组;分别测定大鼠血浆和支气管肺泡灌洗液中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-8含量.结果:与对照组相比,LPS组血浆和支气管肺泡灌洗液中TNF-α、IL-1β和IL-8均明显升高(P均<0.05),而地塞米松治疗组和大黄治疗组则均明显下降(P<0.05或P<0.01).结论:LPS诱导的大鼠ALI表现为肺和全身炎症反应;大黄和地塞米松能减轻肺和全身炎症反应,其机制可能是通过抑制TNF-α、IL-1β和IL-8活性来实现的.     

硫化氢对大鼠内毒素性急性肺损伤炎性细胞因子的影响

目的 观察硫化氢(H2S)对脂多糖(LPS)所致大鼠内毒素性急性肺损伤(ALI)炎性细胞因子的影响,探讨其对肺脏的作用机制.方法 雄性SD 大鼠共48只,随机分为六组,每组8只:空白对照组、LPS 组、LPS+NaHS 低剂量组、LPS+NaHS 中剂量组、LPS+NaHS 高剂量组及LPS+PPG 组.所有大鼠均检测血清中白细胞介素-1β(IL-1β)和IL-10浓度的变化,取肺组织检测肺组织中IL-1β、IL-10、黏附分子-1(ICAM-1)mRNA基因表达变化及肺组织NF-κB p65活性变化.结果 与空白对照组比较,LPS组大鼠血清中IL-1β和IL-10浓度,肺组织中IL-1β、IL-10和ICAM-1 mRNA基因表达和NF-κB p65活性均明显升高(P<0.01).与LPS组比较,LPS+NaHS低、中、高剂量组血清中IL-1β浓度、肺组织中IL-1βmRNA基因表达和NF-κB p65活性均明显降低;LPS+NaHS中、高剂量组血清中IL-10浓度和IL-10 mRNA基因表达明显升高,ICAM-1 mRNA基因表达明显降低(P<0.05或P<0.01).与LPS组比较,LPS+PPG组血清中IL-1β浓度、肺组织中IL-1β和ICAM-1 mRNA基因表达及NF-κB p65活性均明显升高,血清中IL- 10浓度和肺组织中IL-10 mRNA基因表达明显降低(P<0.05或P<0.01).结论 H2S对内毒素诱导的ALI大鼠有保护性作用,其作用机制可能与H2S调节炎性细胞因子的生成有关.     

急性肺损伤大鼠肺组织肝脏X受体α表达的研究

目的 观察内毒素性急性肺损伤(ALI)大鼠肝脏X受体α(LXRα)的改变,探讨LXRα在ALI发病中的作用机制.方法 将48只Wistar大鼠随机均分为两组.采用尾静脉注射脂多糖(LPS)5 mg/kg复制大鼠ALI模型,对照组静脉注射生理盐水2.5 ml/kg.于致伤后1、2、4和8 h取大鼠动脉血进行血气分析及肿瘤坏死因子-α(TNF-α)水平检测;取肺测定肺湿/干重(W/D)比值、髓过氧化物酶(MPO)活性及肺组织病理学改变;用逆转录-聚合酶链反应(RT-PCR)检测肺组织LXRα mRNA、TNF-α mRNA表达;用酶联免疫吸附法(ELISA)检测TNF-α含量变化;用免疫组化法观察肺组织LXRα蛋白表达情况.结果 与对照组比较,ALI组致伤后各时间点动脉血氧分压(PaO2)均显著降低,肺W/D比值、MPO活性均显著升高(P均<0.05);病理观察显示肺组织受损;肺组织LXRα mRNA表达下降,TNF-α mRNA表达升高(p均<0.05),肺组织匀浆和动脉血清中TNF-α亦显著升高,4 h达高峰.免疫组化显示对照组肺组织表达较高水平LXRα蛋白,ALI组在LPS致伤后可见LXRα蛋白表达较对照组显著下降(P均<0.05).结论 正常大鼠肺组织可表达LXRα,LPS可引起ALI大鼠肺组织LXRα的基因和蛋白表达下降,这可能与ALI发病有关.     

单肺通气中肺保护策略研究进展

目的 通过对单肺通气中肺保护策略研究进展的分析,为临床工作提供理论指导,减少单肺通气术中低氧血症和术后肺部并发症的发生.方法 应用计算机在Pubmed上检索2007年1月～ 2012年5月有关单肺通气的文章,检索词为:one lung ventilation,hypoxemia,lungprotection,限定文章语言种类为English.对资料进行初审,并查找全文.纳入标准:①有关单肺通气的实验及临床研究;②有关肺保护的试验研究.排除标准:①综述文献;②重复研究.共收集到200多篇有关单肺通气方面的文献,纳入14篇.结果 纳入的14篇文章中有关单肺通气术中管理方面的文献12篇,有关单肺通气时低氧血症方面的文献2篇.通过对入选文献进行分析、整理,将单肺通气术中管理从通气模式选择、潮气量与呼吸频率的设置、PEEP及CPAP的运用、吸入氧浓度及液体管理等5方面进行分析,归纳总结出目前在单肺通气时的肺保护策略和麻醉管理进展.结论 随着对单肺通气中肺保护的深入研究,单肺通气的麻醉管理将更加有效、合理.     

终末期肺病肺移植术后并发症的影像学表现

目的探讨肺移植术后并发症的影像学改变。方法6例患者进行了同种异体肺移植术,其中4例终末期慢性阻塞性肺疾病患者和1例为中毒性细支气管炎患者接受单肺移植,另1例为外周型肺腺鳞癌并双肺转移接受双肺移植。用胸片及CT观察术后并发症的影像学变化。结果6例肺移植手术全部成功,6例中围手术期3例死亡,3例已存活16~36个月。术后2例发生急性排斥反应,5例出现再移植肺水肿,3例并发肺部感染,2例出现气胸,2例术后1~2个月出现吻合口狭窄。结论及时的胸片和CT检查对肺移植术后并发症的防治有非常重要的指导价值。     

CT引导下经皮穿刺肺活检术诊断肺部弥漫性病变

目的 评价CT引导下经皮穿刺肺活检术在诊断肺部弥漫性病变中的价值.方法 回顾性分析68例接受CT引导下经皮穿刺肺活检术的肺部弥漫性病变患者的资料.主要影像学改变包括弥漫性网状结节或结节、弥漫性线网状影、弥漫性磨玻璃样密度.采用18CT或20G穿刺活检针进行活检.结果 68例患者均一次性穿刺成功,且均能做出明确诊断.其中恶性病变19例,包括细支气管肺泡癌9例,转移癌10例;良性病变49例,为血型播散型肺结核27例,结节病8例,矽肺与煤工肺7例,间质性肺炎2例,肺泡蛋白沉着症4例,过敏性肺炎1例;主要并发症为气胸和出血,并发症的发生率为17.65%.结论 在肺部弥漫性疾病的诊断中,CT引导下经皮肺穿刺肺活检术是一种实用、安全、并发症少、准确性高、创伤小的定性诊断方法.     

Visual anatomical lung CT scan assessment of lung recruitability

Purpose

The computation of lung recruitability in acute respiratory distress syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for preventing lung collapse. The quantitative lung CT scan, obtained by manual image processing, is the reference method but it is time consuming. The aim of this study was to evaluate the accuracy of a visual anatomical analysis compared with a quantitative lung CT scan analysis in assessing lung recruitability.

Methods

Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung recruitment were analyzed. Lung recruitability computed at an airway pressure of 5 and 45?cmH₂O was defined as the percentage decrease in the collapsed/consolidated lung parenchyma assessed by two expert radiologists using a visual anatomical analysis and as the decrease in not aerated lung regions using a quantitative analysis computed by dedicated software.

Results

Lung recruitability was 11.3?% (interquartile range 7.39?C16.41) and 15.5?% (interquartile range 8.18?C21.43) with the visual anatomical and quantitative analysis, respectively. In the Bland?CAltman analysis, the bias and agreement bands between the visual anatomical and quantitative analysis were ?2.9?% (?11.8 to +5.9?%). The ROC curve showed that the optimal cutoff values for the visual anatomical analysis in predicting high versus low lung recruitability was 8.9?% (area under the ROC curve 0.9248, 95?% CI 0.8550?C0.9946). Considering this cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76, and 0.86, respectively.

Conclusions

Visual anatomical analysis can classify patients into those with high and low lung recruitability allowing more intensivists to get access to lung recruitability assessment.     

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury

OBJECTIVE: To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. INTERVENTIONS: After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). CONCLUSIONS: Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.     

人工肺的应用与肺膜材料性能评价

人工肺是在膜两侧进行气体、血液之间交换的场所，一般中空纤维是人工肺的主要部件。膜式人工肺是一种接近人体生理状态，较为理想的人工肺。它以人工合成的高分子材料制备的微孔膜作血液和气体的交换场所，完成人体的生理氧和过程，因而可暂时代替人体肺进行气体交换，用以支持生命以争取心、肺病变治愈及功能恢复的机会。膜式人工肺因选用的高分子材料、微孔膜的形式、血液和气体的流动方式的不同可有多种类型。但是至今还存在着未能解决的问题是与血液相接触的膜材料血液相容性仍不理想。本文从肺的功能出发，分析膜式人工肺的特点，探讨改善膜式人工肺血液相容性的方法及其发展方向     

B-lines quantify the lung water content: a lung ultrasound versus lung gravimetry study in acute lung injury

B-lines (also termed ultrasound lung comets) obtained with lung ultrasound detect experimental acute lung injury (ALI) very early and before hemogasanalytic changes, with a simple, noninvasive, nonionizing and real-time method. Our aim was to estimate the correlation between B-lines number and the wet/dry ratio of the lung tissue, measured by gravimetry, in an experimental model of ALI. Seventeen Na-pentobarbital anesthetized, cannulated (central vein and carotid artery) minipigs were studied: five sham-operated animals served as controls and, in 12 animals, ALI was induced by injection of oleic acid (0.1 mL/kg) via the central venous catheter. B-lines were measured by echographic scanner in four predetermined chest scanning sites in each animal. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio by gravimetry. After the injection of oleic acid, B-lines number increased over time. A significant correlation was found between the wet/dry ratio and B-lines number (r = 0.91, p < 0.001). These data suggest that in an experimental pig model of ALI/ARDS, B-lines assessed by lung ultrasound provide a simple, semiquantitative, noninvasive index of lung water accumulation, strongly correlated to invasive gravimetric assessment.     

Endogenous lung stem cells for lung regeneration

Introduction: Lifelong maintenance of a healthy lung requires resident stem cells to proliferate according to tissue requirements. Once thought to be a quiescent tissue, evolving views of the complex differentiation landscape of lung stem and progenitor cells have broad implications for our understanding of how the lung is maintained, as well as the development of new therapies for promoting endogenous regeneration in lung disease.

Areas covered: This review collates a large body of research relating to the hierarchical organization of epithelial stem cells in the adult lung and their role in tissue homeostasis and regeneration after injury. To identify relevant studies, PubMed was queried using one or a combination of the terms ‘lung’, ‘airway’, ‘alveoli’, ‘stem cells’, ‘progenitor’, ‘repair’ and ‘regeneration’.

Expert opinion: This review discusses how new technologies and injury models have challenged the demarcations between stem and progenitor cell populations.     

Indication for lung biopsy and usefulness of lung biopsy]

The criteria of open lung biopsy for operative indication were determined on the basis of hemodynamics in each congenital cardiac anomalies with pulmonary hypertension. More than 10.6, 8 and 8 units. m2 of pulmonary vascular resistance (PVR) were considered as indication for open lung biopsy in the patients with complete transposition of the great arteries, complete atrioventricular canal defect and atrial septal defect respectively. Lung biopsy should be done in patients with ventricular septal defect when PVR is more than 8 units. m2 and if it is greater than 4 with the oxygen inhalation test or 6 with the Tolazoline test. The usefulness of lung biopsy was also emphasized on the basis of the postoperative result in which lung biopsy diagnosis has been done.