兔肺灌洗型呼吸窘迫综合症模型和猪肺表面活性物质的治疗…

用整肺灌洗法复制兔ＲＤＳ模型，系统观察了灌洗液磷脂和蛋白质含量，血气、潮气量、肺顺应性，生命体征，Ｘ线胸片和病理形态学指标。结果显示；整肺灌洗法可迅速导致严重呼吸窘迫，其病理特征主要是ＰＳ系统功能急剧缺乏和肺务，用猪肺表面活性物质治疗可获得明显改善。     

党参对大鼠RDS模型肺泡表面活性物质含量及板层小体的影响

党参对大鼠ＲＤＳ模型肺泡表面活性物质含量及板层小体的影响甘肃中医学院病理教研室（兰州７３００００）白娟，邱桐，李萍应用党参治疗大鼠呼吸窘迫综合征（ＲＤＳ）的实验研究证明，党参具有改善肺功能的作用。为了进一步研究其作用机理，本文测定了大鼠支气管肺泡灌洗...     

肺表面活性物质蛋白B、C的提纯及生物活性功能分析

目的为了提高肺表面活性物质的疗效及减少异性蛋白造成的免疫反应,我们对猪肺组织中的肺表面活性物质蛋白B和C进行了提取及纯化.方法用生理盐水灌洗猪肺后,经低温离心,萃取,层析来提取肺表面活性物质蛋白B和C,又用高效液相色谱纯化蛋白B和C.并用膜天平测定所提纯的肺表面活性蛋白SP-B和SP-C的生物活性.结果用SDS-聚丙烯酰胺凝胶电泳检测,显示杂蛋白条带明显减少,分子量分别为6.7×1000、17.9×1000.且提纯的蛋白用较好的生物活性.P＜0.05.结论高效液相色谱能在分子水平上纯化肺表面活性物质蛋白B和C,并较好地保持了其生物活性.     

家兔肺表面活性物质缺乏的病理及超微结构研究

用多次肺灌洗法建立肺表面活性物质缺乏模型,分三组进行对比观察。实验组在灌洗后,肺总磷脂、SPC下降为对照组的1/8～1/10肺表面张力明显增高;两侧广泛肺萎陷及多数透明膜形成;电镜的特征性改变为肺泡Ⅲ型细胞变性坏死,板层小体缺失及呼吸膜破坏。此外,对本病的重要性、病理特点及发病机理着重进行了讨论。     

肺表面活性物质研究进展

肺表面活性物质除具有降低表面张力的作用以外，还有稳定呼吸道、抗水肿、促液体弥散、抗粘液胶合、促纤毛运动、抗菌、抗炎、平滑肌松驰等作用。除用于替代治疗呼吸窘迫综合征（ＲＤＳ）外，肺炎、胎粪吸入综合征（ＭＡＳ）、肺囊性纤维化（ＣＦ）、肺纤维化（ＰＦ）、哮喘和肺移植等方面的实验及临床研究正在进行之中     

ARDS时肺泡表面活性物质系统功能异常的机制

成人型呼吸窘迫综合征（ＡＲＤＳ）的肺泡表面活性物质（ＰＳ）系统功能异常已经被确认。现有的研究资料表明，其机制是肺损伤时肺泡Ⅱ型上皮细胞内和肺泡内ＰＳ代谢改变所致的ＰＳ数量和质量的改变，以及肺泡中的一些特殊因子对ＰＳ表面活性的抑制作用。     

中华眼镜蛇毒四个分离组份对呼吸窘迫综合征影响的实验研究

用ＤＥＡＥＳｅｐｈａｄｅｘＡ５０层析柱把眼镜蛇毒分离得４个组份，分别试用于动物的油酸型呼吸窘迫综合征（ＲＤＳ）模型。结果显示：与对照组相比，组份Ⅳ使实验组小鼠的肺系数降低且呈量－效关系；使实验组家兔ＰａＯ２下降幅度减少，支气管－肺泡灌洗液蛋白渗出量减少；组份Ⅳ具有抗补体活性的作用，其缓解油酸型ＲＤＳ的作用可能与此有关。     

不同方法制备的猪肺泡表面活性物质对离体灌洗鼠肺顺应性的改善作用

不同方法制备的猪肺泡表面活性物质对离体灌洗鼠肺顺应性的改善作用广州珠江医院儿科（广州５１０２８２）封志纯，彭宜君，梁巧明，吴凤玲广州珠江医院生物品研究室吴秉毅，冯永清，张帆，谢亚峰动物肺泡表面活性物质（ＰＳ）制备工艺尤在肺组织处理方法上尚有争议。我们...     

肺表面活性物质对大鼠肺损伤后氧合功能的影响

目的和方法：本研究利用氧自由基所致的大鼠肺损伤模型,对肺损伤后肺表面活性物质（ＰＳ）病理改变和外源性ＰＳ替代治疗的作用进行了探讨。结果：大鼠气道滴入黄嘌呤和黄嘌呤氧化酶２４ｈ后,ＰａＯ２和胸肺顺应性显著下降;肺系数明显增高,组织学观察可见炎症性肺水肿。肺支气管灌洗液分析结果表明ＰＳ含量减少,蛋白含量增高。应用外源性ＰＳ治疗后,ＰａＯ２从处理前３２４±８６ｋＰａ上升到４７５±２９ｋＰａ（Ｐ＜００１）。结论：（１）肺损伤后的不同阶段ＰＳ的病理变化可能是不一致的;（２）外源性ＰＳ的替代治疗有明显效果。     

人肺表面活性物质结合蛋白B的研究现状

人肺表面活性物质结合蛋白Ｂ（ＳＰ－Ｂ）为肺泡表面活性物质中的重要成份。具有生物活性的ＳＰ－Ｂ存在于肺泡Ⅱ上皮细胞、肺泡巨噬细胞和肺泡中，在体外ＳＰ－Ｂ与磷脂的复合物即具有肺表面活性物质的大部分生物活性，而在体内可增强肺的顺应性，人ＳＰ－Ｂ基因定位第２号染色体，其基因表达受多种因素调节。遗传性ＳＰ－Ｂ缺乏病例已见报道。     

A case of pulmonary alveolar proteinosis treated with whole lung lavage

Pulmonary alveolar proteinosis represents a rare syndrome characterized by the accumulation of proteinaceous phospholipid-laden material in the alveoli. This leads to impaired gas exchange and arterial hypoxemia of varying degrees. The diagnosis is confirmed by lung biopsy. Sequential whole-lung lavage (WLL) first described in 1963 is the standard of care. We report a case of a male diagnosed of having pulmonary alveolar proteinosis (PAP) on transbroncial lung biopsy (TBLB). He was treated with sequential WLL (Left followed by right, Left being more involved on chest X-ray) followed by recombinant GM-CSF, with good result.     

Variant alveolar lipoproteinosis: a syndrome with distinct clinical and pathological features

Pulmonary alveolar proteinosis (PAP) is a rare condition in which pulmonary macrophages fail to clear surfactant, resulting in the alveolar accumulation of lipoproteinaceous debris. The histopathology of PAP is typified by diffuse filling of terminal airways with eosinophilic, PAS/diastase (PAS/D)-positive acellular material. We present five patients who showed histopathological changes in the lungs consistent with mild PAP. However, these cases were notable for the abundance of degenerating alveolar macrophages, weak PAS staining of lipoproteinaceous material and paucity of lamellated bodies on ultrastructural examination. Only one patient showed the CT finding of mosaiform 'crazy-paving' and the opalescent bronchoalveolar lavage fluid characteristic of PAP. In one case, therapeutic lung lavage based on a presumptive diagnosis of PAP exacerbated respiratory distress. Three patients showed partial or near-complete resolution of disease in response to high-dose corticosteroid therapy, a treatment approach that is generally ineffective in PAP. We conclude that distinguishing 'variant alveolar lipoproteinosis' from classical PAP is clinically important. Despite the otherwise typical appearance of lipoproteinaceous alveolar material in lung biopsies, the presence of degenerating foamy macrophages and atypical histochemical, ultrastructural and radiographic features suggest a steroid-responsive form of proteinosis that is likely pathogenetically distinct and may not be amenable to whole-lung lavage.     

Changes in dead space/tidal volume ratio and pulmonary mechanics after surfactant replacement therapy in respiratory distress syndrome of the newborn infants

This study was performed to elucidate the mechanism of improved oxygenation after surfactant replacement therapy in respiratory distress syndrome (RDS) of the newborn infants. In 26 newborns with RDS, end tidal-CO2 tension (PetCO2), arterial blood gas analysis and pulmonary function tests were measured at baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in dead space/tidal volume ratio (VD/VT ratio=(PaCO2-PetCO2)/PaCO2), oxygenation index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO2) were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A-a)DO2 improved, and VD/VT ratio decreased progressively after surfactant administration, becoming significantly different from the baseline at 30 min and thereafter with administration of surfactant. Pulmonary mechanics did not change significantly during the observation period. VD/VT ratio showed close correlation with OI and (A-a)DO2, but not with pulmonary mechanics. These results suggest that decreased physiologic dead space resulting from the recruitment of atelectatic alveoli rather than improvement in pulmonary mechanics is primarily responsible for the improved oxygenation after surfactant therapy in the RDS of newborn.     

Glycosaminoglycans and glycoproteins in bronchoalveolar lavage fluid from patients with pulmonary alveolar proteinosis

Bronchoalveolar lavage fluid from two cases of pulmonary alveolar proteinosis were analyzed for glycosaminoglycans and glycoproteins. The clinical courses of the two cases were entirely different. In one patient, signs and symptoms recurred despite repeated therapeutic bronchoalveolar lavages. In the other patient, three successive bronchoalveolar lavages brought about complete recovery. It was found that the bronchoalveolar lavage fluid from the former case contained various subtypes of glycosaminoglycans [hyaluronic acid, chondroitin sulfate A(C), dermatan sulfate, and heparan sulfate] and glycoprotein. On the other hand, the bronchoalveolar lavage fluid from the latter case contained glycoprotein, but no detectable amounts of glycosaminoglycans. There was only a slight qualitative difference in glycoprotein of bronchoalveolar lavage fluid between the two cases. The presence or absence of glycosaminoglycans in bronchoalveolar lavage fluid may be related to the prognosis of pulmonary alveolar proteinosis.     

Acute experimental silicosis. Lung morphology, histology, and macrophage chemotaxin secretion.

The acute inflammatory reaction in the lungs of guinea pigs produced by the intratracheal injection of silica was assessed by histologic studies and whole-lung lavage 1, 2, 4, 7, and 14 days after the intratracheal instillation of quartz particles or saline. In addition, lavaged macrophages were cultured in vitro, and the media were assayed for chemotactic factors. This exposure to silica produced a neutrophilic inflammatory response around terminal bronchioles that was well developed within 1 day after injection. Four days after injection, neutrophils were replaced by mononuclear cells; and by 7 days, loosely organized granulomas and collagen deposition were detected in the interstitium. The number of neutrophils (PMNs) recovered by lavage from experimental animals was greatest 1 day after injection and was significantly greater (P less than 0.01) than that for controls at all time points. In contrast, the number of macrophages recovered by lavage did not exceed control levels until 7 days after injection and remained elevated thereafter. Thus, the cells recovered by lavage tended to mirror the changes seen in the inflamed lung. In experiments utilizing blind-well chemotactic chambers, both peritoneal exudate neutrophils and macrophages migrated toward supernatants from cultures of alveolar macrophages lavaged from silica-exposed animals in greater numbers (P less than 0.02) than toward supernatant from control animal macrophage cultures at each time point. Migration of normal alveolar macrophages toward supernatants from all cultures was minimal. Thus, exposure to silica in vivo appears to be a potent stimulus for the release of neutrophil and monocyte chemotactic factors by alveolar macrophages in vitro. The correlation between the types of inflammatory cells identified in the lung both microscopically and by lavage and the chemotactic factors released in vitro by alveolar macrophages from these lungs suggests that alveolar macrophages play a role in mediating pulmonary inflammation in this form of experimental silicosis.     

Immunosuppression of Pulmonary Natural Killer Activity by Exposure to Ozone

Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless involves several cell types and/or products of these cells. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, following 23.5 hours of exposure. NK activity is important for defense against viral, bacterial, and neoplastic disease. The depressed NK activity resulting from continuous ozone exposure could therefore result in a compromised ability to defend against pulmonary diseases.     

Dilemmas about the antenatal use of corticosteroids for prevention of neonatal morbidity and mortality

Neonatal respiratory distress syndrome (RDS) is one of the biggest problems in modern obstetrics. The incidence of RDS is 1%-2%. RDS is a condition of insufficient surfactant production. Surfactant is a complex molecule which is responsible for maturation of fetal lungs. The most important factor for insufficient surfactant production and pulmonary immaturity is shortening of gestation, i.e. preterm delivery. Antenatal corticosteroids for maturation of fetal lungs are in use for over thirty years. Corticosteroids decrease the incidence and intensity of RDS, the severity of intracerebral hemorrhage, and overall neonatal morbidity and mortality. The mechanism of corticosteroid action is probably induction of fetal pulmonary enzyme complex that is responsible for adequate surfactant production and regulation of pulmonary interstitial fluids. In this literature review, we analyze long- and short-term benefits and risks of single and multiple antenatal corticosteroid administration.     

Immunosuppressive effects of CCL17 on pulmonary antifungal responses during pulmonary invasive aspergillosis

Aspergillus fumigatus-sensitized CCR4-deficient (CCR4-/-) mice exhibit an accelerated clearance of conidia during fungal asthma. In the present study, we examined the roles of CCL17 and CCL22, two CCR4 ligands, during pulmonary invasive aspergillosis in neutropenic mice. Kaplan-Meier survival curve analysis revealed that wild-type C57BL/6 (CCR4+/+) mice were significantly protected from the lethal effects of Aspergillus compared with their wild-type controls following systemic neutralization with anti-CCL17 but not anti-CCL22 antibodies. Systemic neutralization of CCL17 significantly increased whole-lung CCL2 levels. Mouse survival and histological analysis revealed that the receptor mediating the deleterious effects of CCL17 was CCR4 since mice genetically deficit in CCR4 (CCR4-/-) did not develop invasive aspergillosis. Enzyme-linked immunosorbent assay analysis of whole-lung samples at day 2 after conidial challenge in neutrophil-depleted CCR4-/- and CCR4+/+ mice revealed that whole-lung IL-12 levels were significantly increased in the CCR4-/- group compared with the wild-type group. Also at day 2 after conidial challenge, significantly greater numbers of CD11c+ F4/80+ and CD11c+/CD86+ but fewer CD3/NK1.1+ cells were present in the lungs of CCR4-/- mice compared with their wild-type counterparts. Thus, CCL17-CCR4 interactions dramatically impair the pulmonary antifungal response against A. fumigatus in neutropenic mice.     

Effects of sensitization to ovalbumin on the lipid content of the bronchoalveolar lavage fluid in guinea pigs

Four groups of guinea-pigs were studied (l1: control, l2: sensitized to ovalbumin, l3: sensitized and challenged by aerosol of ovalbumin, l4: challenged by aerosol of histamine). In urethane anaesthetized guinea-pigs, pulmonary resistances and dynamic compliance were measured (before and after aerosol of ovalbumin in l3 and aerosol of histamine in l4). The lungs were removed and the static pressure-volume curves were performed to determine lung compliance. In the pulmonary lavage fluids, surface tension and total fatty acids and phospholipids were measured by Cahn's electrobalance and gas chromatography respectively. In l2 guinea-pigs, the mean value of total fatty acids and of phospholipids was significantly decreased in pulmonary lavage fluid, by 24.5% and 40.2% respectively. Surface tension was increased while lung mechanics was identical to control. In l3 guinea-pigs, the mean value of total fatty acids and of phospholipids was significantly decreased in pulmonary lavage fluids, by 55.7% and 53.2% respectively. Surface tension was increased. In vivo, lung mechanics was changed: dynamic compliance decreased, pulmonary resistances increased. Pressure-volume curves were flattened and pulmonary compliance of isolated lungs was decreased since bronchial obstruction remained after death. In l4 guinea-pigs, the mean value of total fatty acids and of phospholipids was increased in pulmonary lavage fluid but not significantly, by 26.6% and 9.2%. Surface tension was not changed. Lung mechanics was very significantly affected by bronchospasm, but after death the mechanics of the isolated lung and of control lung was identical. Finally, the decrease of surface-active lipids in pulmonary lavage fluid originates in the sensitization and is enhanced by antigen-induced bronchial anaphylaxis but not by histamine-induced bronchospasm.     

Chorioamnionitis decreased incidence of respiratory distress syndrome by elevating fetal interleukin-6 serum concentration

Respiratory distress syndrome (RDS) of newborns is one of the most important factors determining neonatal morbidity and mortality. The interleukin-6 (IL-6) titre in cord sera of RDS-free neonates born to mothers with histological chorioamnionitis was significantly higher than that in RDS-complicated neonates without chorioamnionitis. Maternal administration of glucocorticoid suppressed the IL-6 concentrations in the cord sera of fetuses with chorioamnionitis. The fetuses without chorioamnionitis who suffered from RDS even after maternal glucocorticoid administration showed a similar IL-6 titre to that of RDS-affected neonates without chorioamnionitis. Examination of the mechanism by which IL-6 decreased the incidence of fetal RDS revealed that H441-4, a human pulmonary adenocarcinoma cell line, stimulated with recombinant (r)-IL-6 started the synthesis of mRNA and protein of pulmonary surfactant protein (SP)-A. The present study shows that IL-6 elevation in fetuses with chorioamnionitis promotes fetal lung maturation by inducing SP-A synthesis, thereby decreasing the incidence of RDS in the preterm neonates.