超声引导羊膜腔内和胎肺注射肺表面活性物质预防早产兔肺损伤的比较

目的 探讨超声引导羊膜腔内和胎肺注射肺表面活性物质（PS）预防早产兔肺损伤的效果比较。 方法 将15只新西兰孕兔随机分为胎肺注射PS组（L组）、羊膜腔内注射PS组（A组）及对照组,每组5只。妊娠第27天注药1h后行剖宫产术,观察各组早产兔存活时间,检测支气管肺泡灌洗液中二棕榈胆碱酯磷酸（DPPC）和白细胞介素-6（IL-6）含量,取肺组织行形态学和生化分析。 结果 与对照组相比,L组和A组早产兔存活时间明显延长,DPPC及SP-A含量增加,肺组织细胞凋亡指数和肺损伤病理评分及IL-6含量降低（P＜0.05）,II型肺泡上皮细胞板层小体增多、内质网肿胀减少。与A组相比,L组早产兔DPPC、SP-A和IL-6含量增加（P＜0.05）,余指标无明显差异。 结论 羊膜腔内和胎肺注射PS均可有效预防早产兔肺损伤,与羊膜腔注射PS相比,胎肺注射等量PS可获得更大效益,有望成为预防早产儿肺损伤的新疗法。     

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.     

Bilateral lavage with diluted surfactant improves lung function after unilateral lung contusion in pigs

OBJECTIVE: This study evaluates the effects of bronchoalveolar lavage with diluted surfactant on unilateral lung contusion-induced lung dysfunction. DESIGN: Randomized prospective animal study. SETTING: An animal laboratory. SUBJECTS: Twenty adult pigs, weighing 25-35 kg. INTERVENTIONS: Animals were randomly assigned to controls and surfactant treatment. Bilateral lavage with surfactant treatment began 30 mins after unilateral lung contusion. Then 25 mg/kg of body weight diluted Curosurf (5 mg/mL) was applied in a volume of 5 mL/kg of body weight. Observation time was 8 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: The Pao2/Fio2 ratio fell from 500 to 250 and then recovered gradually in controls and surfactant-treated pigs. After another 4 hrs, the Pao2/Fio2 ratio deteriorated again in controls, but not in surfactant-treated animals. Total compliance fell by 50% after injury but was completely restored by surfactant treatment. Lung contusion increased the median number of neutrophils in bronchoalveolar lavage fluid from 2% to 30% of total cells and peaked >60% at 480 mins in the contused lungs of control pigs. Surfactant-treated pigs had 40% neutrophils at 480 mins without reaching significant difference to controls. The leukocyte neutral proteinase inhibitor increased to 500 ng/mL at 30 mins postinjury in the contused lungs and increased to 2000 ng/mL after surfactant treatment. CONCLUSIONS: Bilateral bronchoalveolar lavage with diluted surfactant can effectively improve lung function after experimental unilateral lung contusion in pigs.     

Lung fluid balance in lambs before and after premature birth.

The purpose of this study was to see if lung vascular protein permeability is greater in preterm lambs with respiratory distress than it is in lambs without lung disease. We measured pulmonary vascular pressures, lung lymph flow, and concentrations of protein in lymph and plasma of 10 chronically catheterized preterm lambs (gestation 133 +/- 1 d) for 2-4 h before and for 4-8 h after delivery by cesarean section. All lambs were treated with mechanical ventilation after birth and received a constant intravenous infusion of glucose-saline solution at an hourly rate of 10 ml/kg. Respiratory failure developed in six lambs, in which there was a sustained threefold postnatal increase in lung lymph flow and lymph protein flow, with an even greater increase in pleural liquid drainage. Concentrations of protein in lymph and pleural liquid were almost identical, averaging approximately 75% of the plasma protein concentration. In the four preterm lambs without lung disease, lymph flow and lymph protein flow were either near or below fetal values by 6-8 h after birth, and there was little or no pleural liquid drainage. Extravascular lung water averaged 7.3 +/- .8 g/g dry lung in lambs with respiratory failure compared to 4.8 +/- .5 g/g dry lung in lambs without lung disease. Thus, pulmonary edema with abnormal leakage of protein-rich liquid from the lung microcirculation into the interstitium is an important pathological feature of the respiratory disease that often occurs after premature birth.     

Synergistic effect of triiodothyronine and dexamethasone on male and female fetal rat lung surfactant synthesis

It has previously been reported that morphologic and functional indices of fetal lung maturation are delayed in male rabbit fetuses, and these differences cannot be overcome by glucocorticoid treatment. Since thyroid hormone also stimulates surfactant production we have studied the effects of triiodothyronine (T3) and dexamethasone on saturated phosphatidylcholine (SPC) synthesis by day 20 male and female rat lung. Control male lung slices incorporated significantly less 3H-choline into SPC than females; surgery on day 17 markedly stimulated 3H-choline incorporation into SPC by both sexes, but the sex difference persisted. The optimal dose of T3 inhibited SPC synthesis by both sexes while dexamethasone was stimulatory. When T3 and dexamethasone were given together they had a greater effect than that of dexamethasone or T3 alone. Based on these results we conclude that the male deficit in pulmonary surfactant production may be overcome by the synergistic effects of T3 and dexamethasone.     

Live Borrelia burgdorferi preferentially activate interleukin-1 beta gene expression and protein synthesis over the interleukin-1 receptor antagonist.

Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) in human peripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1 beta than IL-1 alpha and sevenfold more IL-1 beta than IL-1ra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1 beta was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains. No difference in induction of IL-1ra was seen between these strains. The marked induction of IL-1 beta was partially diminished by heat-treatment and abrogated by sonication; IL-1ra was not affected. This suggested that a membrane component(s) accounted for the preferential induction of IL-1 beta. However, recombinant outer surface protein beta induced little IL-1 beta. By 4 h after stimulation, B. burgdorferi induced sixfold more IL-1 beta protein than LPS. In contrast to LPS-induced IL-1 beta mRNA which reached maximal accumulation after 3 h, B. burgdorferi-induced IL-1 beta mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-1ra mRNA peaked at 12 h, whereas LPS-induced IL-1ra mRNA peaked at 9 h. IL-1 beta synthesis increased in response to increasing numbers of spirochetes, whereas IL-1ra synthesis did not. The preferential induction by B. burgdorferi of IL-1 beta over IL-1ra is an example of excess agonist over antagonist synthesis induced by a microbial pathogen, and may contribute to the destructive lesion of Lyme arthritis.     

A noninflammatory interleukin-1beta fragment stimulates fetal lung fluid absorption in guinea pigs

We have previously demonstrated that full-length interleukin (IL)-1beta can induce and stimulate lung fluid absorption in near-term guinea pig fetuses via stimulation of fetal cortisol synthesis and release. To develop a potentially clinically useful drug, we tested the hypothesis that maternal administration of a noninflammatory IL-1beta-fragment (IL-1beta(Fr)) induced cortisol synthesis and stimulated lung fluid absorption in preterm fetuses. IL-1beta(Fr) was administered s.c. daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar 5% albumin into the lungs, and lung fluid absorption was measured over 1 h by mass balance. Lung fluid absorption was induced at 61 days and stimulated at 68 days gestation by IL-1beta(Fr), which both were attenuated by cortisol synthesis inhibition. Moreover, induction of labor by oxytocin stimulated lung fluid absorption at 61 days but had no stimulatory effect at 68 days gestation when given with the IL-1beta(Fr). Plasma adrenocorticotropin and cortisol concentrations were increased by IL-1beta(Fr) at 61 days gestation and remained high but unstimulated by IL-1beta(Fr) at 68 days gestation, and metyrapone always reduced cortisol concentrations. Prenatal lung fluid absorption, when present as well as IL-1beta(Fr)-induced, was always propranolol- and amiloride-sensitive, suggesting that beta-adrenoceptor stimulation and the epithelial Na(+) channel (ENaC) were critical for the induced/stimulated lung fluid absorption. ENaC expression was increased by IL-1beta(Fr) and attenuated by cortisol synthesis inhibition. Thus, our results suggest a potential clinical use of IL-1beta(Fr) therapeutically to induce lung fluid absorption in fetuses at risk of preterm delivery.     

Failure to detect an effect of prolactin on pulmonary surfactant and adrenal steroids in fetal sheep and rabbits.

Recent reports have indicated an association between low cord prolactin (PRL) and the occurrence of respiratory distress syndrome in premature infants, and it is reported that PRL administration increases the lecithin content of fetal rabbit lung. We administered 1 mg ovine PRL to 32 rabbit fetuses on day 24 of gestation and evaluated lung phospholipid synthesis and content on day 26. Compared with diluent-injected littermates, PRL had no effect on the rate of choline incorporation into lecithin, tissue content of phospholipid and disaturated lecithin, or plasma corticoids. However, both choline incorporation and corticoids were increased in all animals undergoing surgery compared with unoperated controls. We also infused PRL (1 mg/day, i.v.) into three fetal sheep continuously over five periods of 5-8 days. Although supraphysiologic concentrations of PRL were achieved in plasma and amniotic fluid, there was no effect of this treatment on the flux of tracheal fluid surfactant or on plasma concentrations of corticoids of dehydroepiandrosterone sulfate. Thus, in this study, we failed to detect either a stimulation of the surfactant system or an adreno-corticotropic effect by PRL as previously postulated. This suggests that the relationship between PRL and respiratory distress sundrome is an indirect association.     

Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms.

Acid aspiration lung injury may be mediated primarily by neutrophils recruited to the lung by acid-induced cytokines. We hypothesized that a major acid-induced cytokine was IL-8 and that a neutralizing anti-rabbit-IL-8 monoclonal antibody (ARIL8.2) would attenuate acid-induced lung injury in rabbits. Hydrochloric acid (pH = 1.5 in 1/3 normal saline) or 1/3 normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 or 24 h. In acid-instilled rabbits without the anti-IL-8 monoclonal antibody, severe lung injury developed in the first 6 h; in the long-term experiments, all rabbits died with lung injury between 12 and 14 h. In acid-instilled rabbits given the anti-IL-8 monoclonal antibody (2 mg/kg, intravenously) either as pretreatment (5 min before the acid) or as treatment (1 h after the acid), acid-induced abnormalities in oxygenation and extravascular lung water were prevented and extravascular protein accumulation was reduced by 70%; in the long-term experiments, anti-IL-8 treatment similarly protected lung function throughout the 24-h period. The anti-IL-8 monoclonal antibody also significantly reduced air space neutrophil counts and IL-8 concentrations. This study establishes IL-8 as a critical cytokine for the development of acid-induced lung injury. Neutralization of IL-8 may provide the first useful therapy for this clinically important form of acute lung injury.     

秋冬季节对健康大鼠肺组织表面活性蛋白A和白细胞介素6表达的影响

背景:近年来研究证实,季节气候的变化和肺表面活性物质蛋白A及白细胞介素6在肺脏免疫防御功能调节方面均起到很重要的作用,但是季节气候产生影响的机制目前还不清楚.目的:观察秋冬季大鼠肺组织表面活性蛋白A和白细胞介素6的表达,认识季节和气候变化影响大鼠肺脏非特异性免疫的作用机制,为呼吸系统季节性发病的病理生理机制的认识提供实验依据.方法:分别于立秋、秋分、立冬、冬至节气前14 d购入雄性SD实验大鼠,并分为相应组别.自由摄取水及正常饲料和室温饲养,接受自然光照.到相应节气,于当日下午6时将动物断头处死,取出全肺组织作表面活性蛋白AmRNA和白细胞介素6 mRNA检测.结果与结论:与立秋、秋分、冬至组大鼠相比,立冬大鼠肺组织表面活性蛋白A和白细胞介素6均表达量较低,提示肺部免疫防御功能存在秋季高冬季低的季节节律,而表面活性蛋白A和白细胞介素6正是免疫防疫功能的物质基础.     

Surfactant nebulisation: lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits

Objective: Surfactant nebulisation is a promising alternative to surfactant instillation in newborns with the respiratory distress syndrome. Although less surfactant is deposited in the lung, it improves gas exchange, probably due to a superior distribution. We hypothesize that a more uniform distribution of nebulised surfactant results in a more uniform pulmonary blood flow and consequently a more efficient gas exchange. We asked whether the pulmonary blood flow changes after surfactant replacement, and to what extent pulmonary blood flow is influenced by the amount of surfactant deposition. Furthermore, we investigated whether sufficient nebulised surfactant is deposited in the lungs to achieve a sustained improvement in lung function. Interventions: Surfactant was nebulised or instilled, or saline was nebulised, in 18 lung-lavaged rabbits. After 2 h the rabbits were weaned from mechanical ventilation to continuous positive airway pressure, 40 % oxygen. We measured blood gasses, dynamic lung compliance, surfactant distribution using 99 m technetium nanocoll label, and the pulmonary blood flow distribution, using microspheres. Results: Partial pressure of oxygen in arterial blood and lung compliance were significantly higher after surfactant nebulisation than after saline nebulisation. Surfactant instillation gave a superior effect with respect to these variables. Nebulised surfactant was distributed more uniformly over the lungs than instilled surfactant. Although pulmonary blood flow changed over time, it remained uniformly distributed following both modes of surfactant treatment. Surfactant deposition was neither strongly related to pulmonary blood flow nor strongly related to the change in blood flow. Conclusions: Although nebulised surfactant is uniformly distributed, we can provide no evidence that this results in a more uniform pulmonary blood flow distribution. Therefore, other than a superior surfactant distribution, no additional reason was found for the efficient gas exchange after nebulisation.     

Thyroid hormone stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung.

To investigate the mechanism of thyroid hormone action on pulmonary surfactant synthesis, we characterized the effect of triiodothyronine on phosphatidylcholine synthesis in cultured fetal rabbit lung. Since glucocorticoids stimulate surfactant synthesis and reduce the incidence of Respiratory Distress Syndrome in premature infants, we also examined the interaction of triiodothyronine and dexamethasone. The rate of choline incorporation into phosphatidylcholine was determined in organ cultures of rabbit lung maintained in serum-free Waymouth's medium. In 23-d lung cultured for 72 h, the increase in choline incorporation with triiodothyronine alone, dexamethasone alone, and triiodothyronine plus dexamethasone was 50, 62, and 161%, respectively. Both triiodothyronine and dexamethasone also increased incorporation rates with glucose, glycerol, and acetate as precursors, and stimulation with triiodothyronine plus dexamethasone was at least additive. Dexamethasone, but not triiodothyronine, affected distribution of radioactivity from [3H] acetate among phospholipids. Stimulation was first detected 8-12 h after addition of triiodothyronine, and then increased in a linear fashion. With triiodothyronine plus dexamethasone, stimulation was maximal at 48-72 h, and was supra-additive at all times. Exposure of cultured lung to dexamethasone enhanced the subsequent response to triiodothyronine, but not vice versa. When triiodothyronine was removed from cultures, there was no further stimulation and the triiodothyronine effect was partially reversed within 24 h. Half-maximal stimulation of choline incorporation occurred at a triiodothyronine concentration (0.10 nM) very similar to the dissociation constant for triiodothyronine binding to nuclear receptor (0.11 nM). The relative potencies of thyroid hormone analogs for nuclear binding and stimulation of phosphatidylcholine synthesis were also similar: triiodothyroacetic acid greater than triiodothyronine-proprionic acid greater than L-triiodothyronine approximately D-triiodothyronine much greater than thyroxine much greater than 3,5-diethyl-3'-isopropyl-DL-thyronine approximately 3,5-dimethyl-3'-isopropyl-L-thyronine approximately reverse triiodothyronine. The effect of triiodothyronine was blocked by the presence of either actinomycin D or cycloheximide, inhibitors of ribonucleic acid and protein synthesis, respectively. We conclude that triiodothyronine stimulates phosphatidylcholine synthesis by a process involving nuclear receptors and de novo ribonucleic acid and protein synthesis. These findings support the concept that endogenous triiodothyronine has a physiologic role in lung maturation and suggest that a combined antenatal therapy with thyroid hormone and glucocorticoid may be useful for prevention of Respiratory Distress Syndrome in the premature infant.     

Regulatory effects of endogenous interleukin-1 receptor antagonist protein in immunoglobulin G immune complex-induced lung injury.

IL-1 receptor antagonist (IL-1Ra) has regulatory effects on IL-1 activity both in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered human IL-1Ra suppressed neutrophil recruitment and ensuing lung injury. In this study, we sought to determine if endogenous rat IL-1Ra might regulate this lung-inflammatory response. By Northern blot analysis of lung mRNA and Western analysis of bronchoalveolar lavage (BAL) fluids, rat IL-1Ra expression was found to increase during development of inflammation in IgG immune complex-mediated alveolitis. By immunostaining, alveolar macrophages and recruited neutrophils were the apparent sources of IL-1Ra. In vivo blocking of endogenous IL-1Ra resulted in a 53% increase in lung vascular permeability and a 180% increase in BAL fluid neutrophils. In companion studies, a significant increase in IL-1beta was found, whereas no significant change in TNF-alpha activity was observed. Whereas the in vivo regulatory effects of IL-1R appear to be limited to IL-1beta, IL-10 regulates both IL-1beta and TNF-alpha in this model, reflected by a 48% increase in BAL IL-1beta in rats treated with anti-IL-10. These findings suggest that IL-1Ra is an intrinsic regulator of inflammatory injury after deposition of IgG immune complexes and that it regulates production of IL-1beta.     

Randomised comparison of partial liquid ventilation, nebulised perfluorocarbon, porcine surfactant, artificial surfactant, and combined treatments on oxygenation, lung mechanics, and survival in rabbits after saline lung lavage

OBJECTIVE: To compare gas exchange, lung mechanics, and survival to 12 h in surfactant-depleted lung-injured rabbits, treated with partial liquid ventilation (PLV) with perfluorocarbon, nebulised perfluorocarbon, and porcine or artificial surfactant. DESIGN: Prospective randomised controlled study. SETTING: Animal laboratory, University of Edinburgh, UK. SUBJECTS: Eighty-two adult female New Zealand white rabbits with surfactant deficiency and acute lung injury induced by repeated saline lavage. INTERVENTIONS: Animals were randomised to one of seven treatments: (a) control (n = 20); (b) PLV with perfluorocarbon PF 5080 (n = 12); (c) nebulised PF 5080 (n = 10); (d) artificial surfactant (n = 10); (e) porcine surfactant (n = 10); (f) artificial surfactant+PLV (n = 10); (g) porcine surfactant+PLV (n = 10). MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and dynamic compliance (Cdyn) were measured hourly until 12 h. Oxygenation was improved by PLV, porcine surfactant, porcine surfactant+PLV and artificial surfactant+PLV. Cdyn improved after treatment with PLV, porcine surfactant and PLV+porcine surfactant. Survival was greater with PLV and artificial surfactant+PLV. Neither nebulised PF 5080 nor artificial surfactant had a detectable effect. CONCLUSIONS: PLV, porcine surfactant and combinations of surfactant with PLV improved oxygenation, Cdyn and survival, but none was clearly superior to the others.     

急性肺损伤兔肺泡灌洗液及血清肿瘤坏死因子α、白细胞介素1β和白细胞介素6浓度变化与小剂量高渗盐水的干预

目的:观察创伤性休克兔经小剂量高渗盐水治疗后肺部炎症反应及病理学损伤的变化情况,进一步研究高渗盐水对创伤应激状态下急性肺损伤的作用及其机制。方法:实验于2005-08/2006-04在华中科技大学同济医学院附属同济医院急诊科实验室完成。①实验分组:新西兰白兔30只随机分为3组:假手术组、生理盐水处理组、高渗盐水治疗组,每组10只。②实验方法:假手术组:局部麻醉下行插管术及肝素化,静脉输注平衡盐80mL。生理盐水处理组:用骨钳致兔一侧股骨中下1/3粉碎性骨折,经股动脉放血至储血瓶内,使平均动脉压降至(40±5)mmHg,45min后输注生理盐水4mL/kg,再回输储血及2倍于失血量的平衡盐液进行复苏。高渗盐水治疗组:除以75g/L的氯化钠溶液代替生理盐水外,其余处理同生理盐水处理组。在休克前、休克末、复苏后2h、4h分别采集静脉血1mL备用。复苏后4h空气栓塞处死动物,进行支气管肺泡灌洗,收集支气管肺泡灌洗液。③评估指标:双抗体夹心ELISA法测定支气管肺泡灌洗液以及血清肿瘤坏死因子α、白细胞介素1β、白细胞介素6的浓度;凝胶电泳迁移率改变分析法检测肺泡巨噬细胞核蛋白提取物中核因子κB的活性;显微镜观察肺组织的病理改变。结果:30只实验动物均进入结果分析。①血清细胞因子浓度的变化:与假手术组比较,生理盐水处理组肿瘤坏死因子α浓度在休克发生后迅速升高(P<0.05),复苏后又进一步上升(P<0.01),白细胞介素1β及白细胞介素6浓度在复苏后4h才有明显增加(P<0.01)。高渗盐水治疗组与生理盐水处理组比较,复苏后2～4h肿瘤坏死因子α、白细胞介素1β及白细胞介素6浓度均有不同程度下降(P<0.05,P<0.01,P<0.05)。②支气管肺泡灌洗液细胞因子浓度的变化:生理盐水处理组肿瘤坏死因子α、白细胞介素1β及白细胞介素6浓度均显著高于假手术组(P均<0.01),高渗盐水治疗组各细胞因子的浓度虽然也高于假手术组(P<0.05,P<0.01,P<0.01),但与生理盐水处理组比较均有明显降低(P<0.05,P<0.01,P<0.01)。③肺泡巨噬细胞核因子κB的活性变化:生理盐水处理组核因子κB的活性远高于假手术组(P<0.01),而高渗盐水治疗组核因子κB的活性虽然也高于假手术组(P<0.01),但与生理盐水处理组比较有显著降低(P<0.01)。④肺组织病理学改变:高渗盐水治疗组肺水肿及炎性细胞浸润明显减轻;Ⅰ、Ⅱ型肺泡上皮细胞内仅有少量空泡,上皮基本完整,基底膜增厚不明显。结论:小剂量高渗盐水治疗可抑制创伤性休克时核因子κB的活化,减少促炎细胞因子的合成与分泌,减轻肺部的炎症反应,从而发挥对急性肺损伤的保护作用。     

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide

Objective: To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI).¶Design: Prospective, randomised, controlled experimental study.¶Setting: A medical university hospital research laboratory.¶Intervention: Twenty-nine adult rabbits (2.4–3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs.¶Measurements and results: All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO₂/FIO₂ from 520 ± 30 to 395 ± 19 mmHg and dynamic compliance (Cdyn) from 1.20 ± 0.11 to 0.73 ± 0.05 ml/cmH₂O × kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 ± 0.8 % to 12.9 ± 1.0 % (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO₂/FIO₂, Cdyn and Qs/Qt after 6 h were 301 ± 15 mmHg, 0.67 ± 0.05 ml/cmH₂O × kg and 16.5 ± 0.8 %, compared to 224 ± 26 mmHg, 0.53 ± 0.04 ml/cmH₂O × kg and 24.1 ± 2.0 %, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected.¶Conclusion: Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.     

肺表面活性物质相关蛋白A在肺癌组织中的表达及意义

目的研究肺表面活性物质相关蛋白A（SPA）在肺腺癌和鳞状细胞癌组织中的表达及其临床意义。方法应用免疫组化EnVision二步法,检测27例肺腺癌、15例鳞状细胞癌组织中SP—A的表达,并分析其与临床病理诸因素之间的关系。结果SP-A在肺腺癌、鳞状细胞癌组织中的阳性表达率分别为51．85％、6．67％,腺癌组织中SP—A的表达明显高于鳞状细胞癌组织（P〈0．01）。SP—A在乳头状腺癌、细支气管肺泡癌、腺泡性腺癌和黏液性腺癌组织中的表达率依次为85．71％、50％、40％和25％。SP-A的表达与患者性别、年龄、肿瘤直径大小和淋巴结转移均无关。结论SPA的表达可能与肺癌的组织学类型有关,可作为鉴别肺腺癌与鳞状细胞癌的参考指标。     

联合检测宫颈阴道分泌物中胎儿纤维连接蛋白及白介素-6对早产的预测价值

目的 探讨宫颈阴道分泌物中胎儿纤维连接蛋白(fFN)及白介素-6(IL-6)的联合检测对早产的预测价值.方法 选取2013年2月-2014年2月在南京市妇幼保健院住院治疗的45例先兆早产孕妇设为观察组,同期正常孕妇50例设为对照组.观察2组宫颈阴道分泌物中fFN、IL-6表达水平差异,不同妊娠结局孕妇上述指标差异及其相互关系.结果 观察组宫颈阴道分泌物中fFN及1L-6表达水平均显著高于对照组(P＜0.01);95例孕妇中,妊娠结局为早产者29例,足月产者66例.早产孕妇上述指标显著高于足月产者(P＜0.01);联合检测fFN和IL-6预测先兆早产敏感度为91.11％,特异度为42.00％;预测妊娠结局的敏感度和特异度分别为93.10％及59.09％;相关性分析表明fFN与IL-6显著正相关(r=0.839,P＜0.01).结论 宫颈阴道分泌物中fFN和IL-6表达水平是预测早产的较敏感指标,联合检测可提高临床预测早产及妊娠结局的能力.