磷脂酶A2在内毒素致大鼠肺损伤中的作用

大鼠静脉注射大肠杆茵内毒素（３０ｍｇ／ｋｇ）后３ｈ肺血管外水量和支气管肺泡灌洗液中蛋白浓度明显增加,表明发生了通透性肺水肿;同时血清和支气管肺泡灌洗液中磷脂酶Ａ２（ＰＬＡ２）活性升高,且ＰＬＡ,活性的升高与肺血管外水量的增加呈显著正相关。预先给予ＰＬＡ２抑制剂对溴苯酰基溴可抑制内毒素引起的ＰＬＡ２活性升高和通透性肺水肿。提示ＰＬＡ２介导了内毒素引起的肺损伤。     

急性缺氧暴露不同时间家兔血浆心钠素、抗利尿激素、醛固酮的变化

本实验观察了８０只家兔在急性缺氧６、１２、２４、３６、４８、６０、７１ｈ后肺指数、血浆心钠素（ＡＮＰ）、抗利尿激素（ＡＶＰ）、醛固酮（ＡＬＤ）及尿量的变化。结果表明：在缺氧２４－７２ｈ,肺指数明显升高,尿量减少;缺氧１６ｈ,血浆ＡＮＰ明显升高;而缺氧４８和６０ｈ无ＡＮＰ升高现象。缺氧７２ｈ,血浆ＡＮＦ又明显高于缺氧前水平;血浆ＡＶＰ只在缺氧２４ｈ明显升高;血浆ＡＬＤ未见显著性变化。这些结果提示：在缺氧状态下,ＡＮＰ、ＡＶＰ的释放均与缺氧暴露的时间有关。这些激素的平衡失调可能与急性缺氧性肺水肿的发生有关。     

营养不良性肺水肿大鼠肺泡液体清除机制的研究

目的探讨营养不良性肺水肿大鼠肺泡液体清除功能的变化及其机制。方法制备营养不良性肺水肿大鼠动物模型,分别于48h和120h测定大鼠肺泡液体清除率（AFC）、总肺水量（TLW）和肺血管外水量（EVLW）。将钠通道阻断剂氨氯毗眯、Na-K-ATP酶阻断剂畦巴因及β2受体激动剂特布他林分别灌注到正常及禁食120h大鼠的肺泡腔内,测定AFC的变化。结果大鼠禁食48hAFC（19．7±3．22％）与正常大鼠AFC（18．5±2．21％）比较没有明显变化;120h时AFC（9．50±2．19％）明显降低。氨氯吡咪、哇巴因明显降低营养不良性肺水肿大鼠AFC（P＜0．05）,特布他林对营养不良性肺水肿大鼠AFC的作用与对照组大鼠比较差异无显著性（P＞0．05）。结论营养不良性肺水肿与钠通道及Na-K-ATP酶及的活性被抑制,导致肺泡液体清除能力降低有关。     

急性缺氧暴露不同时间家兔血浆心钠素,抗利尿激素,醛固…

本实验观察了８０只家兔在急性缺氧６、１２、２４、４８;６０、７１ｈ后肺指数、血浆心钠素（ＡＮＰ）、抗利尿激素（ＡＶＰ）、醛固酮（ＡＬＤ）及尿量的变化。结果表明：在缺氧２４－７２ｈ,肺指数明显升高,尿量减少、缺氧１６ｈ,血浆ＡＮＰ明显升高;而缺氧４８和６０ｈ无ＡＮＰ升高现象。缺氧７２ｈ,血浆ＡＮＦ又明显高于缺氧前水平;血浆ＡＣＰ只在缺氧２４ｈ明显升高;血浆ＡＬＤ未见显著性变化。这些结果提示：在缺氧状     

肺血管EDNO及其合酶在大鼠低氧性肺动脉高压形成中的作用

本研究观察了低氧对大鼠肺组织和血管内皮一氧化氮合酶（ＮＯＳ）活性及内皮衍生一氧化氮（ＥＤＮＯ）依赖性舒张反应的影响,以及ＮＯＳ抑制剂（Ｌ－ＮＡＭＥ）对常氧和低氧大鼠肺组织和血管内皮ＮＯＳ活性及颈、肺动脉血压（ＣＡＰｓ、ｍＰＡＰ）的作用。结果表明常氧大鼠肺泡内无肌性血管内皮未见ＮＯＳ活性,其肺血管床对ＥＤＮＯ依赖性舒血管物质ＢＫ没有反应,注射Ｌ－ＮＡＭＥ后大鼠ｍＰＡＰ略有降低,ＣＡＰｓ有所升高。低氧大鼠肺泡内无肌性血管内皮显示ＮＯＳ活性,对ＢＫ的ＥＤＮＯ依赖性舒张反应呈剂量依赖性增大,注射Ｌ－ＮＡＭＥ使低氧大鼠ｍＰＡＰ显著降低（Ｐ＜０．０１）,ＣＡＰｓ显著升高（Ｐ＜０．０５）。提示肺血管ＥＤＮＯ及其合酶在维持正常成年大鼠肺循环低压低阻中的生理作用值得进一步探讨;低氧引起肺血管内皮ｅｃＮＯＳ活性增加和ＥＤＮＯ生成增多可能起到限制肺动脉压过度升高的调制作用,也可能对肺血管内皮产生毒性作用,反而促进肺动脉高压的发生和发展。     

高原鼢鼠和高原鼠兔肺细叶的结构特征

高原鼢鼠和高原鼠兔是青藏高原土著动物,对低氧具有很好的适应性.为了探讨在低氧环境中两者肺细叶结构的适应特征,应用体视学方法测量了肺细叶相关指标.结果发现 :高原鼢鼠和高原鼠兔肺单位面积肺泡数显著高于SD大鼠,单个肺泡面积和弹性纤维/肺实质比显著低于SD大鼠;高原鼢鼠肺泡隔厚度最厚,高原鼠兔最薄,且三种动物具显著差异; 高原鼢鼠和高原鼠兔气-血屏障的算术平均厚度(Ta)和调和平均厚度(Th) 均显著低于SD 大鼠;在三个级别的微血管中,高原鼠兔中膜肌层厚度显著低于高原鼢鼠,两种高原动物均显著低于SD大鼠;高原鼢鼠和高原鼠兔的微血管密度(MVD)显著高于SD大鼠.以上结果表明,高原鼢鼠和高原鼠兔肺细叶结构特征表现出一定趋同,这些特征有利于在低氧条件下提高肺气体扩散容量;但是,肺泡隔厚度和微血管中膜肌层厚度/血管外径比又表现出明显的差异,可能是不同生境造成的[动物学报 54(3):531-539,2008].     

外源性肺表面活性物质替代治疗对烟雾吸入所致肺组织细胞损害的影响

目的：探讨使用外源性肺表面活性物质（ＰＳ）治疗能否减轻烟雾吸入所致肺组织细胞损害。方法：Ｗｉｓｔａｒ大鼠随机分为５组：Ⅰ组,正常对照;Ⅱ组,烟雾吸入;Ⅲ组,烟雾＋ＰＳ＋机械通气（ＭＶ）;Ⅳ组,烟雾＋盐水＋ＭＶ;Ⅴ组,烟雾＋ＭＶ,伤后５ｍｉｎ经气管导管注入ＰＳ（１００ｍｇ／ｋｇ）或等量盐水,ＭＶ４ｈ,观察２４ｈ,检测动脉血气、肺水量、支气管肺泡灌洗液（ＢＡＬＦ）中白细胞分类计数及乳酸脱氢酶（ＬＤＨ）、血管紧张素转换酶（ＡＣＥ）和碱性磷酸酶（ＡＫＰ）活性、胎盘型碱性磷酸酶（ＰＬＡＰ）含量、肺泡壁纤维成分含量及病理检查等。结果：Ⅱ组伤后发生呼吸衰竭、肺水肿及肺部急性炎症反应,ＢＡＬＦ中ＬＤＨ、ＡＫＰ、ＡＣＥ和ＰＬＡＰ水平均明显升高,肺泡壁纤维成分含量显著减少。Ⅲ组血气较Ⅱ组明显改善,但ＢＡＬＦ中各酶水平、肺泡壁纤维成分含量及肺部炎症、水肿等无显著减轻。Ⅳ、Ⅴ组治疗无效。结论：烟雾吸入伤早期外源性ＰＳ治疗能一定程度改善呼吸功能,但对肺组织细胞损害无明显保护作用,不能减轻继发性炎症反应和急性肺水肿     

急性热应激小鼠血浆心钠素、血管紧张素及其体液Na+/K+的变化

观察了小鼠在热应激以及热应激恢复期血浆心钠素（ＡＮＰ）,血管紧张素（ＡⅡ）及其体液中Ｎａ＾＋／Ｋ＾＋的变化。结果表明,经热应激后小鼠血浆ＡＮＰ含量无明显变化,ＡＩＩ含量则明显上升,Ｎａ＾＋／Ｋ＾＋明显减少,肺指数也明显升高,而在热应激的恢复期,小鼠血浆ＡＮＰ却极显著上升,为对照组的２５０％,而ＡⅡ却极显著下降,为对照组的４７％,尿Ｎａ＾＋／Ｋ＾＋值仍持续降低,而肺指数却回降么正常水平,这些结果揭示     

血管钠肽、 C型钠尿肽和心房钠尿肽舒血管作用的对比

本实验采用离体血管灌流方法,观察和比较血管钠肽（ＶＮＰ）,Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）对大鼠肺动脉,腹主动脉和腹腔静脉的舒张作用。．结果表明,ＶＮＰ,ＣＮＰ和ＡＮＰ对离体大鼠的保留内皮与去内皮的肺动脉,腹主动脉和腹腔静脉均有浓度依赖性舒张作用。     

大鼠胸部照射后支气管肺泡灌洗液成分和肺组织纤溶活力的变化

大鼠胸部照射γ射线２０Ｇｙ,照射后观察支气管肺泡灌洗液（ＢＡＬＦ）中蛋白质含量、细胞总数和分类及巨噬细胞存活率,肺指数及肺组织纤溶活力,并做了大体解剖和组织学检查。结果为：照射后２周开始ＢＡＬＦ中蛋白质含量、细胞总数和中性粒细胞即明显增多,照射后１——２个月持续处于高水平,高峰在１．５─２个月,照射后３─４个月有所下降,肺指数有相应变化;肺组织纤溶活力则相反,从照射后２周开始持续下降,至照射后２个月已降至最低,接近于零。形态学观察也见到有早期肺水肿和晚期肺萎缩等变化。由上结果可见,大鼠胸部照射后的早期主要为渗出性病变和纤溶活力的降低。文中讨论了照射后血管内皮细胞的损伤在放射性肺损伤发病中的作用。     

Protective effect of endogenous beta-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice

Some investigators have reported that endogenous beta-adrenoceptor tone can provide protection against acute lung injury. Therefore, we tested the effects of beta-adrenoceptor inhibition in mice with acute Escherichia coli pneumonia. Mice were pretreated with propranolol or saline and then intratracheally instilled with live E. coli (10(7) colony-forming units). Hemodynamics, arterial blood gases, plasma catecholamines, extravascular lung water, lung permeability to protein, bacterial counts, and alveolar fluid clearance were measured. Acute E. coli pneumonia was established after 4 h with histological evidence of acute pulmonary inflammation, arterial hypoxemia, a threefold increase in lung vascular permeability, and a 30% increase in extravascular lung water as an increase in plasma catecholamine levels. beta-Adrenoceptor inhibition resulted in a marked increase in extravascular lung water that was explained by both an increase in lung vascular permeability and a reduction in net alveolar fluid clearance. The increase in extravascular lung water with propranolol pretreatment was not explained by an increase in systemic or vascular pressures. The increase in lung vascular permeability was explained in part by anti-inflammatory effects of beta-adrenoceptor stimulation because plasma macrophage inflammatory protein-2 levels were higher in the propranolol pretreatment group compared with controls. The decrease in alveolar fluid clearance with propranolol was explained by a decrease in catecholamine-stimulated fluid clearance. Together, these results indicate that endogenous beta-adrenoceptor tone has a protective effect in limiting accumulation of extravascular lung water in acute severe E. coli pneumonia in mice by two mechanisms: 1) reducing lung vascular injury and 2) upregulating the resolution of alveolar edema.     

High surface tension pulmonary edema induced by detergent aerosol

The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema.     

Effects of continuous positive-pressure ventilation in experimental pulmonary edema.

We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.     

Effect of different levels of positive end-expiratory pressure on lung water content

To compare the effects of 2-, 5-, and 10-cmH2O positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV), pulmonary blood volume (PBV), pulmonary dry weight (PDW), and distensibility, we separately ventilated perfused dogs' lungs in situ and produced pulmonary edema with oleic acid (0.06 ml/kg). Three groups were studied: I, PEEP, 5 cmH2O in both lung; II, PEEP, 2 cmH2O in one lung and 10 cmH2O in the other; and III, PEEP, same as II, but the chest was rotated to compensate for differences in heights. The PEWV and distensibility were less (P less than 0.05) in lungs exposed to 10-cmH2O than to either 2- or 5-cmH2O PEEP. After chest rotation, the difference between 10- and 2-cmH2O PEEP on PEWV was eliminated but that on distensibility was not. We conclude that 10-cmH2O PEEP 1) decreased water content because of lung volume-induced effects on intravascular hydrostatic pressure and 2) improved distensibility by recruitment of alveoli, irrespective of PEWV.     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

模拟高原环境下高原肺水肿大鼠模型的建立

目的在人工实验舱模拟高原环境下,探讨建立高原肺水肿大鼠模型的条件。方法 Wistar大鼠,雌雄各半,随机分为5组:空白对照组、低氧24 h组、低氧48 h组、低氧72 h组、低氧7 d组,测定大鼠肺组织含水量,肺组织中TNF-α、IL-6含量及病理改变。结果与正常对照组相比,低氧24、48、72 h组大鼠肺组织含水量依次为(81.58±0.86)%、(82.13±0.57)%、(82.21±0.88)%,高于正常对照组(78.72±0.52)%,肺组织中IL-6依次为(329.30±133.58)、(323.92±127.42)、(506.29±197.19)pg/mL,TNF-α依次(221.08±20.26)、(208.05±20.33)、(244.63±51.53)pg/mL,高于正常对照组IL-6(187.26±69.49)pg/mL,TNF-α为(91.81±22.24)pg/mL。低氧7d组肺组织含水量(81.47±0.65)%、肺组织中IL-6(241.33±83.60)pg/mL、TNF-α(109.99±31.98)pg/mL,均显著低于低氧72h组,病理学结果显示72h组肺组织有炎性细胞浸润,肺泡壁有明显的充血和水肿。结论模拟海拔5000 m环境,建立大鼠肺水肿模型的较好的时间为72 h。     

Atrial natriuretic peptide clearance receptor agonist lowers pulmonary pressure in hypoxic rats

We demonstrated previously that intravenous administration of exogenous atrial natriuretic peptide (ANP) lowers mean pulmonary arterial pressure (MPAP) in hypoxia-adapted rats. To test the hypothesis that endogenous ANP may also lower MPAP in this model, C-ANP-(4-23), a ring-deleted analogue of ANP that binds to the biologically silent ANP clearance receptor (C-ANP receptor) but not to the ANP biological receptor (B-ANP receptor), was administered intravenously as a bolus injection (10 micrograms/kg) followed by an infusion (1 micrograms.kg-1.min-1 for 60 min) to rats adapted to hypoxia (10% O2) for 4 wk and to air control rats. C-ANP-(4-23) significantly lowered MPAP in hypoxic rats but not in air controls. A statistically insignificant reduction in mean systemic arterial pressure was found in both groups after C-ANP-(4-23) administration. C-ANP-(4-23) significantly (two- to threefold) increased endogenous plasma ANP levels in both groups; the increase was not significantly different between groups. Both basal and post-C-ANP-(4-23) levels of plasma ANP were greater in hypoxia-adapted animals than in air controls; the C-ANP-induced increase in plasma ANP was not significantly different between groups. These results suggest that the endogenous ANP may modulate pulmonary vascular tone in rats with hypoxic pulmonary hypertension.     

Role of hemodynamics and vagus nerves in development of fibrin-induced pulmonary edema

The rapid development of pulmonary edema that may occur in the rabbit after the intracisternal injection of a mixture of fibrinogen and thrombin has classically been considered to result from a vagally mediated increase in vascular permeability (G. R. Cameron and S. N. De, J. Pathol. Bacteriol 61: 375, 1949) and to not be dependent on hemodynamic mechanisms. We tested this hypothesis by evaluating the relationship between the degree of pulmonary hypertension and postmortem extravascular lung water content (EVLW) in both nonvagotomized (n = 10) and vagotomized (n = 7) rabbits administered thrombin (0.1 ml, 500 U/ml) and fibrinogen (1 ml, 27 mg/ml) intracisternally. No increase in EVLW was observed in either group unless pulmonary arterial pressure (Ppa) exceeded 25 Torr, and large increases in EVLW were only observed at higher Ppa's. These results thus indicate that some degree of pulmonary hypertension is required for the development of this form of edema. Because the vascular pressure required to produce edema in this model approaches that required to increase pulmonary vascular permeability in the rabbit, a pressure-dependent increase in permeability may be a common characteristic of neurogenic pulmonary edema in this species. Vagotomy had no protective effect but instead appeared to increase the amount of edema development for a given degree of pulmonary hypertension.     

Pulmonary blood volume and edema in postpneumonectomy lung growth in rats

After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr-labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain.