异丙酚和异氟醚后处理对内毒素血症大鼠肺泡液体转运功能的影响

目的 建立内毒素血症大鼠模型,应用异丙酚和异氟醚,以肺组织湿干重比、肺泡液体清除率、肺水通道1为指标,观察肺泡液体转运功能的变化.方法 健康SD大鼠32只,随机分为4组.生理盐水组:尾静脉注射生理盐水;内毒素组、异丙酚组和异氟醚组均静注内毒素.1小时后.异丙酚组泵注异丙酚,异氟醚组持续异氟醚吸入.2小时后取标本,测定肺组织湿干重比、肺泡液体清除率:Western blot法检测水通道1蛋白.结果 各组肺组织湿/干比差异均尤统计学意义.异氟醚组肺泡液体清除率(0.054±0.007)较异丙酚组(0.065±0.006)高;异氟醚组水通道1为(0.53±0.06)较异丙酚组(0.60±0.07)高,均有显著差异(P＜0.05).结论 与异丙酚相比,异氟醚后处理增加内毒素血症大鼠肺泡液体清除率和水通道1蛋白表达.     

雾化吸入氟化碳对脂多糖性肺损伤大鼠肺内AQP-1及钠钾ATP酶活性的影响

目的观察雾化吸入氟化碳（perfluorocarbon,PFC）对急性肺损伤（acute lung injury,ALI）大鼠肺水肿、肺内水通道蛋白-1（AQP-1）及钠钾ATP酶活性的影响。方法大鼠腹腔注射脂多糖（lipopolysaccharide,LPS）建立ALI模型并雾化吸入PFC进行干预。在LPS注射后6h观察PFC对ALI大鼠动脉血气、肺损伤评分、肺湿干质量比值、肺泡通透指数及钠钾ATP酶活性等的影响,并采用western-blot观察肺内AQP-1表达的变化。结果LPS性肺损伤以肺水肿为主要表现之一。雾化吸入PFC可以缓解LPS诱导ALI后的低氧血症,降低ALI大鼠的肺损伤评分、肺湿干质量比值、肺泡通透指数,同时增加肺组织钠钾ATP酶活性及AQP-1的表达。结论雾化吸入PFC减轻LPS性肺损伤大鼠肺水肿,上调肺损伤期间钠钾ATP酶活性与AQP-1表达。     

羧甲基壳聚糖对肺泡液体清除率的作用研究

目的探讨羧甲基壳聚糖与肺泡液体清除率(Alveolar fluid clearance,AFC)之间的关系,阐明羧甲基壳聚糖是否参与了肺上皮液体转运。方法应用酶标仪测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果羧甲基壳聚糖气管内给药对AFC无明显抑制作用。结论羧甲基壳聚糖可能不影响肺泡上皮钠主动转运机能,抑制肺水肿液的吸收。     

肺水肿的治疗

肺水肿是液体在肺内蓄积而引起的一种症状。通常,心源性肺水肿的发病机理如下: 随着心功能的恶化——如在急性心肌梗塞时——左心室的排出量降低,造成左心室舒张末压升高。这一压力的升高波及到左心房、肺静脉,最终达肺毛细血管。于是,肺毛细血管“微孔”的孔径和通透性增加,肺毛细血管流体静力压亦增加,导致肺间质液体蓄积。间质神经末稍受到刺激而出现呼吸急促,肺泡和呼吸道出现水肿后,由于肺含气量减少和呼吸阻力增加,呼吸功能进一步恶化并导致低氧血症。低氧血症通过水肿液     

甲醛喷雾吸入急性肺水肿大鼠血浆总抗氧化能力的变化

目的探讨甲醛喷雾吸入诱导大鼠急性肺水肿后血浆总抗氧化能力的变化。方法大鼠随机分为对照组和甲醛组,甲醛组大鼠放入鼠笼并置于正方形染毒箱(0·4m×0·4m×0·4m)中盖好,四角放置200g钠石灰,加氧泵连接导管插入盛有200ml的40%甲醛原液的1000ml烧杯通气,每隔25min向箱内喷入甲醛雾化汽一次,让大鼠持续吸入高浓度甲醛诱发急性肺水肿,2h后取出大鼠置于箱外通风处,5h后眼球取血肝素抗凝测定血浆总抗氧化能力,大鼠处死称体重及心、肺重量,计算心肺系数和体肺系数。生理盐水对照组大鼠处理同上,但甲醛换为生理盐水。结果甲醛组肺肿大,边钝圆,切开可见粉红色液流出;与生理盐水对照组比较,甲醛组心肺系数显著增大(2·55±0·32比1·58±0·10,P<0·01),肺指数也显著增大(9·49±1·19比4·67±0·34,P<0·01),血浆T-AOC明显升高(13·8±4·1比7·2±1·2,P<0·01)。结论甲醛吸入后肺水肿形成,大鼠血浆总抗氧化能力升高并可能与应激有关。     

氯喹对烟雾吸入伤大鼠肺微血管通透性的影响

目的探讨氯喹对烟雾吸入伤大鼠肺微血管通透性的影响。方法健康Ｗｉｓｔａｒ大鼠随机分成正常对照组，吸入伤１，３，５，１２，２４ｈ组及氯喹治疗６ｈ和１２ｈ组。肺含水量用干湿重法测定，肺微血管通透性用１３１Ｉ－白蛋白渗出量表示，肺出血量用９９Ｔｃ标记的红细胞出量表示。结果烟雾吸入伤后肺水含量、１３１Ｉ－白蛋白渗出量明显增加，至伤后６ｈ达峰值（Ｐ＜０．０１），而肺内９９Ｔｃ红细胞出量以伤后１ｈ最明显，伤后２４ｈ仍明显高于正常对照组（Ｐ＜０．０１），氯喹治疗伤后６ｈ组，上述指标明显低于吸入伤６ｈ组（Ｐ＜０．０１）。结论氯喹可以明显降低烟雾吸入伤大鼠肺微血管通透性。     

创伤性湿肺

创伤性湿肺是指由于各种创伤所致的急性进行性缺氧性呼吸衰竭。其主要病理特征为肺小血管损伤和通透性增加,导致弥漫性肺水肿和肺泡萎陷,临床表现为难以缓解的低氧血症和进行性呼吸窘迫。 创伤性湿肺这一名称首先由Burford.T.H等根据胸外伤后呼吸困难的病理变化于1945年提出,     

硝苯地平对肺泡液体清除率的作用研究

目的探讨硝苯地平与肺泡液体清除率(AFC)之间的关系,进一步阐明硝苯地平所致非心源性肺水肿发生的病理生理学机制。方法应用酶标仪测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果硝苯地平气管内给药对AFC无明显抑制作用,为(49±5)%。结论临床上硝苯地平引起的非心源性肺水肿可能不是通过调节肺泡上皮钠主动转运机能,抑制肺水肿液的吸收而起作用的。     

血管外肺水对实验性急性肺损伤肺水肿程度判断的价值研究

既往的研究已经证实急性肺损伤(ALI)的病理变化是肺毛细血管渗透性增加导致肺间质水肿,肺内分流增加,氧合下降.肺水肿程度是影响动脉血氧分压和预后的重要因素,既往对肺水肿没有直接的观测指标,自从发明了动脉轮廓法血流动力学检测(PiCCO)后,派生了血管外肺水(EVLW)这个直接反映肺水肿程度的指标.我们采用PiCCO导管检测EVLW,并与重力法肺水测定值进行比较,以验证EVLW反映肺水肿的准确程度.     

SRI63—441对内毒素和血小板激活因子致肺损伤作用的影响

大鼠颈外静脉注射内毒素和血小板激活因子(PAF)均可诱发严重肺水肿,肺血管外水量,肺泡灌洗液中蛋白浓度、细胞计数和多形核粒细胞分类均显著增高。PAF受体拮抗剂SRI63—441对内毒素和PAF所致肺水肿和肺泡灌洗液细胞学变化有部分改善作用。     

A rat model of smoke inhalation injury

Context: Smoke inhalation injury is the leading cause of acute respiratory failure in critical burn victims. Advances in the treatment of smoke inhalation injury have been limited in the past years. To further explore the pathogenesis, stable and practical animal models are necessary.

Objective: To develop a rat model of smoke inhalation injury.

Materials and methods: The smoke composition including the particulate matters, irritant gases, chemical carcinogens was measured. The blood gas values, pro-inflammatory and protein concentration in bronchoalveolar lavage fluid and lung wet to dry weight ratio were assayed. Pathological evaluations of pulmonary were performed at 24 h, 96 h, 7 days and 28 days post-injury. Masson–Goldner trichrome staining was performed on day 7 and 28 post-injury, along with the measurement of hydroxyproline and collagen I and III.

Results: In our present animal model, smoke inhalation caused a significant hypoxemia and CO poisoning. A surge of pro-inflammatory response and microvascular hyperpermeability with neutrophils accumulations were also found in our animal model. At 24 h post-smoke inhalation, the hematoxylin and eosin results exhibited that there were inflammatory exudates and diffuse hemorrhage in the lung tissue with significant edema. With the time going, the lung injuries appeared at alveolar collapse and alveolar septum thickening, which indicated that smoke inhalation further induced damage to lung parenchyma. Specially, the markedly collagen deposition appeared at 28 days post-injury indicated that pulmonary fibrosis happened.

Discussion and conclusion: In conclusion, this rat smoke inhalation injury model induced by our novel self-made smoke generator could be used for acute and chronic lung injury experiments.     

雾化吸入和腹腔注射依达拉奉对烟雾吸入性损伤肺模型大鼠保护作用的比较研究

目的:比较雾化吸入和腹腔注射依达拉奉对烟雾吸入性肺损伤模型大鼠急性肺损伤的保护作用。方法:将30只雄性SD大鼠按照随机数字表法分为正常对照组(A组)、致伤空白组(B组)、致伤腹腔注射治疗组(C组)和致伤低、高剂量雾化吸入治疗组(D、E组),每组6只。B~E组大鼠均被置于含松木屑的烟雾发生器中复制烟雾吸入性肺损伤模型;A组大鼠除不放松木屑外,其余操作同上。造模后30 min,C组大鼠腹腔注射依达拉奉18 mg/kg(每间隔70 min重复1次,共4次);D、E组大鼠雾化吸入依达拉奉9、18 mg/kg(雾化吸入10 min,每间隔60 min重复1次,共4次);A、B组大鼠不作任何处理。末次给药后6 h,进行大鼠动脉血气分析,并计算大鼠肺湿干比(W/D)和肺组织含水率;采用双抗体夹心酶联免疫吸附测定(ELISA)法检测其血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-10含量;采用ELISA等方法检测其肺组织中丙二醛(MDA)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、胱天蛋白酶3(Caspase-3)含量;采用苏木精-伊红染色法观察其肺组织病理改变;采用TUNEL法检测其肺组织细胞凋亡率。结果:A组大鼠肺组织未见异常;B组大鼠肺组织中可见出血及水肿,肺泡结构难以辨认,并可见炎症细胞和红细胞浸润;C~E组大鼠肺组织上述症状均有不同程度改善。与A组比较,其余组大鼠动脉氧分后和吸入氧浓度比值(PaO2/FiO2)以及肺组织SOD含量均显著降低(P<0.05);肺含水率、W/D,血清TNF-α、IL-6、IL-10含量以及肺组织MDA、MPO、Caspase-3含量和细胞凋亡率均显著升高(P<0.05)。与B组比较,各给药组大鼠动脉PaO2/FiO2以及血清IL-10含量均显著升高(P<0.05);肺含水率、W/D,血清TNF-α、IL-6含量以及肺组织MDA、MPO、Caspase-3含量和细胞凋亡率均显著降低,且呈剂量依赖性(P<0.05)。结论:依达拉奉对烟雾吸入性肺损伤模型大鼠具有一定的保护作用,可剂量依赖性地减少炎症介质和(或)细胞因子的产生及释放、减轻过氧化损伤并抑制细胞凋亡,且雾化吸入较腹腔注射的效果更明显。     

硫酸特布他林干粉吸入剂制备工艺的优化研究

目的:优化硫酸特布他林干粉吸入剂的制备工艺。方法:采用喷雾干燥技术制备硫酸特布他林干粉吸入剂,采用双层液体碰撞器测定其体外肺沉积率,扫描电镜观察干粉的表观形貌,热重分析仪测定干粉的水分含量,激光粒度测定仪测定粒径大小,以产品收率、水分含量、粉末的空气动力学粒径及体外肺沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果:通过正交试验-多指标综合评价,最佳制备工艺为:喷雾压力190 kPa,干燥风速0.7 m3.min-1,供液速度7.0 mL.min-1,入口温度120℃。结论:按最佳制备工艺制得的干粉收率为50.54%,水分含量为0.467%,空气动力学粒径为1.80μm,体外肺沉积率为55.19%。正交试验结合多指标综合评价法用于硫酸特布他林干粉吸入剂制备工艺的优化有效可用。     

Effects of terbutaline sulphate aerosol on bronchodilator response and lung mucociliary clearance in patients with mild stable asthma

Ventilatory function and whole lung mucociliary clearance have been assessed in 10 patients with mild stable asthma following inhalation of 1 mg of the beta-adrenergic receptor agonist terbutaline sulphate (Bricanyl, Astra Pharmaceuticals) from a metered dose inhaler (MDI). Compared to placebo inhalation, terbutaline produced marked bronchodilatation (mean percentage increase in FEV1 14%, P less than 0.01). Mucociliary clearance (measured by the in vivo radioaerosol technique) was assessed on three occasions--control, followed by placebo or terbutaline studies in a double-blind, cross-over manner. Particles were removed from the lung at a similar rate in all three studies. The mean (+/- s.e. mean) percentage of aerosol retained in the lungs after 6 h was 58 +/- 5%, 57% +/- 5% and 57 +/- 4% for control, placebo and drug studies respectively. It is concluded that terbutaline sulphate, given as a 1 mg acute dose, does not enhance mucociliary clearance in mild stable asthmatics, although it produces marked bronchodilatation.     

Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs

Because it was still uncertain whether a stimulation of beta1-adrenoceptors accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of denopamine, a selective beta1-adrenergic agonist, on alveolar fluid clearance was determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue labeled albumin instilled into the alveolar spaces over 1 h at 37 degrees C in isolated rat lungs. The principle results were as follows: 1) Although lung water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of denopmaine was similar to that of terbutaline, a selective beta2-adrenergic agonist. In summary, denopamine is a potent stimulator of alveolar fluid clearance in rats exposed to hyperoxia.     

Indices of antioxidant status in rats subjected to wood smoke inhalation and/or thermal injury

The present study investigated antioxidant status in lavage fluid, lung, liver, heart and kidney in a rat model to simulate an inhalation injury as might be encountered by firefighters and burn victims. Anesthetized rats received either a 20% total body surface area (TBSA) full thickness scald or a sham burn. After a 5 h recovery period, half of the animals in the burn or sham burn groups were exposed to cooled western bark (fir and pine) smoke for 16.25 min. The remaining rats in each group breathed room air. At 1, 12, 24, 48 and 96 h after exposure to the smoke, five rats from each of the four groups were euthanatized and lungs were lavaged by infusing three 5 ml aliquots of normal saline for evaluation of airway cellular content and lung wet to dry weight ratios to estimate lung water content. A second series of five rats/group per time point were euthanatized at the above times and lung, liver, kidney and heart were removed for evaluation of tissue antioxidant enzyme activities and for thiobarbituric acid reactive substances (TBARS) concentrations, as well as for lung histology. Smoke exposure resulted in average plasma carboxyhemoglobin (COHb) of 19+/-2% in the two smoke exposed groups and produced areas of erosion of the tracheal surface, resulting in loss of epithelium and exposed basement membrane. Lung water content was not significantly different among the four groups during the 96-h experimental period. Lung TBARS levels were 2-3-fold higher at 12 h in smoke exposed rats compared with controls. These levels peaked at 24 h and remained significantly elevated at 48 h compared to controls. TBARS were also elevated in liver, but not in heart or kidney in response to burn or combined injury. Minor effects on lung antioxidant enzyme activities were observed after smoke inhalation. These data suggest that smoke inhalation, independent of burn injury, induces an oxidant stress that persists for at least the first 48 h after smoke exposure.     

咪达唑仑对小鼠肺泡上皮液体清除作用的研究

目的探讨咪达唑仑与在体小鼠肺泡液体清除率(AFC)之间的关系,以及β2肾上腺素受体激动剂特布他林对其作用的影响。方法应用酶标仪测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果气管内注入0.1mmol/L咪达唑仑后,能显著降低小鼠AFC。与1mmol/L阿米洛利(特异性钠通道阻断剂)合用后抑制效应未见进一步增强,表明咪达唑仑能够抑制与上皮钠通道有关的阿米洛利敏感性AFC。β2肾上腺素受体激动剂特布他林能明显增加小鼠AFC,与咪达唑仑合用后,特布他林几乎完全逆转咪达唑仑对AFC的抑制作用。结论临床上对合并肺脏损害的患者应用咪达唑仑时应考虑其可能对肺脏液体清除作用的影响,必要时可以考虑应用β2肾上腺素受体激动剂特布他林进行治疗。     

Assessment of oxidative stress in lungs from sheep after inhalation of wood smoke

To elucidate potential dose-dependent mechanisms associated with wood smoke inhalation injury, the present study evaluated antioxidant status and the extent of pulmonary injury in sheep after graded exposure to smoke. Adult, male sheep (n=4-5 per group) were anesthetized and received 0, 5, 10 or 16 units of cooled western pine bark smoke, corresponding to 0, 175, 350 and 560 s, respectively, of smoke dwell time in the airways and lung. Smoke was mixed at a 1:1 ratio with 100% O2 to minimize hypoxia. Plasma and expired breath samples were collected pre-smoke, and 6, 12, 18, 24, 36 and 48 h after smoke exposure. Sheep were euthanatized 48 h after smoke exposure and lung and airway sections were evaluated histologically for injury and biochemically for indices of oxidative stress. Plasma thiobarbituric acid reactive substances (TBARS) were 66 and 69% higher than controls after moderate and severe smoke exposure at 48 h, whereas total antioxidant potential was not statistically different among groups at any time after exposure. Lung TBARS showed a dose-dependent response to smoke inhalation and were approximately 2-, 3- and 4-fold higher, respectively, than controls after exposure to 5, 10 and 16 units of smoke. Lung myeloperoxidase (MPO) activity was also higher in smoke-exposed animals than controls, and MPO activity was markedly elevated (19- and 22-fold higher than controls in right apical and medial lobes) in response to severe smoke exposure. Smoke exposure also induced a dose-dependent injury to tracheobronchial epithelium and lung parenchyma. Taken together these data show that few indices of oxidative stress responded in a dose-dependent manner to graded doses of smoke inhalation, although most of the indices measured in lung were affected by the highest dose of smoke. Additional time course studies are necessary to determine whether these oxidants are a cause or a consequence of the airway and lung injury associated with exposure to wood smoke.     

Comparative efficacy of different methods of nebulising terbutaline

The efficacy of terbutaline inhaled from different aerosol systems was studied in 13 adult asthmatics. Terbutaline 1 mg was delivered from a pressurised aerosol, 1 and 4 mg were inhaled from a nebuliser, 1 mg was inhaled through a pressurised aerosol with a pear-shaped, 750 ml spacer, and 1 mg was inhaled from a nebuliser with Intermittent Positive Pressure Ventilation (I.P.P.V.). An open, randomized, cross-over design was used. The bronchodilator effect was evaluated by recording hourly flow-volume curves and the FEV1.0 for 5 h after treatment. No significant difference in bronchodilatation was observed after inhalation of 1 mg terbutaline from different aerosol systems, except following use of the nebuliser, which required approximately four times as much terbutaline to obtain the same effect as the ordinary spray.