血必净对油酸诱导大鼠急性肺损伤的保护作用

目的探讨血必净对油酸诱导急性肺损伤(acute lung injury,ALI)的可能作用机制。方法健康SPF级雄性Wistar大鼠45只,随机分为三组(n=15):A组注射生理盐水作为正常对照;B、C两组所有大鼠均用油酸复制ALI模型,B组为模型对照组,C组在模型基础上加用血必净为治疗组。三组均于注射后12h抽动脉血作血气分析测定血氧分压,确定模型成功后,A、B两组经尾静脉注射生理盐水,C组经尾静脉给予血必净,给药7d,各组于给药后第1天、7天、14天分别处死5只大鼠,取肺组织、心脏血及左肺行支气管肺泡灌洗,肺组织病理学检查并检测灌洗液及血清Ⅲ前胶原(PCⅢ)含量。结果与A组相比,B、C两组动脉血氧分压(PaO2)明显下降(P<0.05),但A、B两组间差异无统计学意义(P>0.05),与A组相比B、C组各时点血清和灌洗液PCⅢ明显增高(P<0.05),肺组织病理学改变均明显,C组与B组相比各时点血清和灌洗液中PCⅢ浓度降低(P<0.05),组织病理学改变明显减轻。结论血必净可能通过抑制ALI炎症反应和肺纤维化对肺损伤起保护作用。     

一种新颖的油酸诱导乳猪急性肺损伤动物模型

目的 采用间断小剂量油酸注射方法,构建符合肺损伤标准、血流动力学稳定的乳猪急性肺损伤动物模型.方法 中华小型猪6只,经右心耳插管注射油酸-乙醇溶液0.1 mL/kg,0.1 mL/次,间隔90 s直至注射完毕.注射过程中监测循环、呼吸参数;实验结束取右下肺组织标本行组织病理检查.结果 油酸注射前、后心率、平均动脉压、平均肺动脉压、心输出量、动脉血氧分压、动脉血二氧化碳分压、pH值、氧合指数差异均有统计学意义(P＜0.05).组织病理显示双肺呈弥漫性改变.结论 小剂量间断注射油酸可构建血流动力学稳定并符合肺损伤诊断标准的急性肺损伤动物模型.     

急性肺损伤早期抗凝疗法的研究

采用骨髓提取液静脉注射建立家兔急性肺损伤的动物模型。实验组在实验过程中使用肝素进行抗凝治疗，对照组不进行抗凝治疗。两组动物同时观察生命体征，血液气体分析，Ｘ线胸片，及肺病理学检查，分析早期抗凝疗法对急性肺损伤以及由此继发的全身脏器损害的影响。     

急性肺损伤动物模型

急性肺损伤是临床常见的一种综合征,病死率较高。研究急性肺损伤的病理、生理过程,明确其发病机制,可为相关治疗策略提供指导和帮助。建立一种理想的急性肺损伤动物模型,有助于研究其发病机制。     

急性肺损伤动物模型

急性肺损伤是临床常见的一种综合征,病死率较高。研究急性肺损伤的病理、生理过程,明确其发病机制,可为相关治疗策略提供指导和帮助。建立一种理想的急性肺损伤动物模型,有助于研究其发病机制。     

急性肺损伤和急性呼吸窘迫综合征的支持治疗

急性呼吸窘迫综合征（ＡＲＤＳ）至今仍缺乏有效治疗,与其相关的病死率仍在５０％以上〔１〕。目前治疗ＡＲＤＳ及急性肺损伤（ＡＬＩ）的一般原则包括：治疗导致ＡＲＤＳ和ＡＬＩ的基础疾病,排除感染因素（所有ＡＬＩ和ＡＲＤＳ的患者,都应该怀疑有感染）,除外弥散性肺炎（一般要求用支气管镜、支气管肺泡灌洗、经支气管肺活检３种方法排除）,支持治疗（包括机械通气、体位治疗、血流动力学管理、血管活性药物的应用、实验性药物治疗、继发性并发症的防治等）。其中支持治疗仍是治疗的关键和重点。本文就有关ＡＬＩ和ＡＲＤＳ的支持治…     

红花黄色素对油酸致大鼠急性肺损伤的保护作用

目的 观察红花黄色素对油酸型急性肺损伤大鼠的保护作用.方法尾静脉注射油酸0.13 g·kg~(-1)制作大鼠急性肺损伤模型,造模前30 min给予各治疗药物或生理盐水,实验在北京安贞医院动物房和药理研究室完成.109只健康Wistar大鼠随机分为正常对照组(n=16)、模型组(n=18)、三个红花黄色素组:290 ms/kg(n=18),170mg/kg(n=20),100ms/kg(n=18)和阳性对照药山莨菪碱30 ms/kg组(n=18).油酸损伤5 h后处死动物,光镜、电镜观察肺组织显微及超微结构病理变化,称重法计算肺指数及A指数、B指数,ELISA检测血浆中炎症因子IL-1β,IL-6含最.实验数据以(x±s)表示,采用SPSS 10.0软件对数据进行正态性、方差齐性检验后行单因素方差分析.以P<0.05为差异具有统计学意义.结果 与正常组[(41.3±1.9),(14.2±0.6),(2.99±0.15),(111±22)μg/L,(2.50±46)μg/L]相比,模型组肺指数、A指数、B指数及血浆IL-1β,IL-6含量[(56.8±4.5),(20.0±1.8),(4.18±0.30),(143±52)μg/L,(302±64)μg/L]显著升高(P<0.01,P<0.05);肺泡壁增厚,肺间质水肿,肺间质和肺泡腔内有红细胞及炎症细胞浸润,染色质凝集于核周边,板层小体空泡化.与模型组相比,3个红花黄色素组和山莨若碱组肺组织病理学损伤明显减轻,染色质无凝集或轻微凝集,板层小体空泡化程度减轻;肺指数、A指数、B指数及血浆IL-1β、IL-6含量显著降低(P<0.01,P<0.05),其中红花黄色索290 ms/ks组上述指标分别为(50.3±6.4),(17.5±2.2),(3.73±0.35),[(106±30)μg/L],[(224±52)μg/L],显著低于模型组(P<0.01).结论 红花黄色素对油酸引起的大鼠急性肺损伤具有保护作用.     

急性肺损伤动物模型

急性肺损伤是临床常见的一种综合征,病死率较高。研究急性肺损伤的病理、生理过程,明确其发病机制,可为相关治疗策略提供指导和帮助。建立一种理想的急性肺损伤动物模型,有助于研究其发病机制。     

吸入米力农对油酸诱导大鼠急性肺损伤的作用

摘要：目的 观察超声雾化吸入米力农对油酸诱导大鼠急性肺损伤（acute lung injury，ALI）的影响。方法 采用静脉注射油酸复制ALI大鼠模型。将40 只SD 大鼠随机分为4 组:对照组（I组）、ALI组（II组）、米力农雾化吸入高剂量组（III组）和米力农雾化吸入低剂量组（IV组）。实验过程中每隔60分钟记录大鼠血压（BP）、肺动脉压（PAP），测定动脉血气和混合静脉血气。注射油酸240分钟后检测肺湿干比(W/D)、髓过氧化物酶（myeloperoxidase，MPO），并且对肺组织进行光镜和电镜观察。结果 超声雾化吸入米力农组中由于注射油酸引起的PAP升高、肺内分流(Qs/Qt)增加和PaO2/FiO2下降均得到缓解，高剂量组更为明显。各治疗组肺W/D 和MPO均比对照组降低，高剂量组更为明显。光镜和电镜观察III、IV组肺损伤有不同程度改善。 结论 米力农雾化吸入能够缓解油酸引起的低氧血症，有效改善ALI多项指标。其对ALI的治疗作用具有剂量依赖性。     

红花黄色素对油酸致大鼠急性肺损伤的保护作用

Objective To investigate the inhibition of safflor yellow on acute lung injury induced by oleic kg-1 mixed with 0.4% bovine serum albumin,while the drugs or normal saline were. injected 30 minutes before-hand. The experiment was made in the Animal Lab and the Pharmacology Lab of Beijing Anzhen Hospital. One hundred and nine healthy Wistar rats were randomly divided into six groups: normal control group (n = 16), mod-of oleic acid injection. The lung morphological changes were observed by optical microscopy and electron mi-croscopy, plasma IL-1β and IL-6 levels were determined by ELISA, lung index, A index and B index were mea-sured. The data were expressed as (x±s) and analyzed by One-Way ANOVA after normality and homogeneity-of-variance tests by SPSS 10.0 software. A P value less than 0.05 indicated statistical significance. Results L-1], the lung index, A index, B index as well as the plasma levels of IL-1β and IL-6 [(56.8±4.5), (20.0± 0.01 or P < 0.05), and tho lung morphological changes were obvious, such as: alveolar septum widened, edema existing in interstitial spaces, etc. In the three SY groups and the anisedamine group, the lung morphological changes were ameliorated; the three indexes and the levels of IL-1β and IL-6 were significantly reduced (P < 0.01 or P < 0.05), compared with the model group. Conclusions SY significantly inhibited oleic acid induced lung inflammation in rats.     

氧合指数的影响因素及其在急性肺损伤诊断中的作用

目的探讨吸入氧浓度(FiO2)和呼气末气道正压(PEEP)对氧合指数(OI)以及急性肺损伤(ALI)、急性呼吸窘迫综合征(ARDS)诊断的影响。方法监测FiO2=100%、PEEP=0时满足ARDS诊断标准模型犬(10只)和患者(10例)在不同FiO2(PEEP=0,FiO2=100%、FiO2=60%、FiO2=21%或FiO2=30%)和PEEP水平(FiO2=100%,PEEP=0·5cmH2O、PEEP=10cmH2O)时OI的变化。结果OI随着FiO2的降低或PEEP的增高而增大,其中FiO2由60%降至21%(患者为30%)或PEEP由5cmH2O升至10cmH2O时OI的变化最显著(P<0·05);同时随着OI的增大,满足ARDS诊断标准的例数逐渐减少,而符合ALI诊断标准的例数增多,甚至出现OI>300mmHg不再符合ARDS或ALI诊断的现象。结论FiO2和PEEP对OI影响显著,从而直接影响ALI、ARDS的诊断结果。因此ALI、ARDS诊断时应严格限定FiO2和PEEP。     

Biomarkers in acute lung injury: insights into the pathogenesis of acute lung injury

Studies of potential biomarkers of acute lung injury (ALI) have provided information relating to the pathophysiology of the mechanisms of lung injury and repair. The utility of biomarkers remains solely among research tools to investigate lung injury and repair mechanisms. Because of lack of sensitivity and specificity, they cannot be used in decision making in patients with ALI or acute respiratory distress syndrome. The authors reviewed known biomarkers in context of their major biologic activity. The continued interest in identifying and studying biomarkers is relevant, as it provides information regarding the mechanisms involved in lung injury and repair and how this may be helpful in identifying and designing future therapeutic targets and strategies and possibly identifying a sensitive and specific biomarker.     

樟柳碱和山莨菪碱预防急性肺损伤的实验研究

目的　探讨樟柳碱和山莨菪碱对急性肺损伤（ＡＬＩ） 的预防作用及其机制。方法　将５０ 只Ｗｉｓｔａｒ 大鼠随机分成５ 组：生理盐水组,油酸模型组,地塞米松预防组,樟柳碱预防组,山莨菪碱预防组。各预防组在注入油酸前３０ 分钟分别于腹腔内注入地塞米松２ ｍｇ／ｋｇ,樟柳碱２ ｍｇ／ｋｇ,山莨菪碱１０ ｍｇ／ｋｇ。以上各组均在注油酸后４ 小时采血测超氧化物歧化酶（ＳＯＤ） 、脂质过氧化物（ＬＰＯ）,观察肺组织病理形态学变化。结果　樟柳碱和山莨菪碱预防组血浆ＬＰＯ含量［（９－０９ ±２－０７）μｍｏＩ／Ｌ和（８－６７±２－１０）μｍｏＩ／Ｌ］ 与油酸模型组血浆ＬＰＯ含量［（１２－１８±１－６７）μｍｏＩ／Ｌ］ 比较均明显降低（ Ｐ均＜ ０－０１）。病理组织学观察示樟柳碱和山莨菪碱预防组肺组织病理改变较油酸模型组减轻。结论　樟柳碱、山莨菪碱能改善油酸致ＡＬＩ的氧自由基及肺的病理形态学变化,对ＡＬＩ有预防作用。     

Dynamic alveolar mechanics in four models of lung injury

Objective To determine whether pathological alterations in alveolar mechanics (i.e., the dynamic change in alveolar size and shape with ventilation) at a similar level of lung injury vary depending on the cause of injury.Design and setting Prospective controlled animal study in a university laboratory.Subjects 30 male Sprague-Dawley rats (300–550 g).Interventions Rats were separated into one of four lung injury models or control (n=6): (a) 2% Tween-20 (Tween, n=6), (b) oleic acid (OA, n=6), (c) ventilator-induced lung injury (VILI, PIP 40/ZEEP, n=6), (d) endotoxin (LPS, n=6). Alveolar mechanics were assessed at baseline and after injury (PaO₂/FIO₂ <300 mmHg) by in vivo microscopy.Measurements Alveolar instability (proportional change in alveolar size during ventilation) was used as a measurement of alveolar mechanics.Results Alveoli were unstable in Tween, OA, and VILI as hypoxemia developed (baseline vs. injury: Tween, 7±2% vs. 67±5%; OA: 3±2% vs. 82±9%; VILI, 4±2% vs. 72±5%). Hypoxemia after LPS was not associated with significant alveolar instability (baseline vs. injury: LPS, 3±2 vs. 8±5%).Conclusions These data demonstrate that multiple pathological changes occur in dynamic alveolar mechanics. The nature of these changes depends upon the mechanism of lung injury.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

肺表面活性物质在急性油酸性肺损伤时的变化

目的：探讨肺表面活性物质（ＰＳ）系统在急性油酸（ＯＡ）性肺损伤时变化的作用机制。方法：３６只新西兰白兔经麻醉、气管切开插管后给予机械通气。动物随机分成２组（每组１８只）,即油酸致急性肺损伤组（ＯＡ组）和生理盐水对照组（ＮＳ组）。观察１、２和４小时（各时间点动物均为６只）,监测静态胸肺总顺应性（ＴＲＣ）、肺功能残气量（ＦＲＣ）、动脉血氧分压（ＰａＯ２）和血清肺表面活性物质蛋白Ａ（ＳＰ－Ａ）浓度,测定     

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。     

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

BACKGROUND:

Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms.

METHODS:

Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa).

RESULTS:

TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05).

CONCLUSIONS:

There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.KEY WORDS: Hyperbaric oxygen, Ischemia-reperfusion injury, Apoptosis     

Effects of positive end-expiratory pressure on the sigmoid equation in experimental acute lung injury

Objectives To describe inflation and deflation volume-pressure (V-P) curves of the respiratory system by the sigmoidal equation at different levels of positive end-expiratory pressure (PEEP) in acute lung injury.Design Experimental study.Setting Physiological laboratory in a university setting.Subjects Six pigs of 25 kg each.Interventions Acute lung injury was induced by oleic acid. PEEP was applied from 0 to 15 cmH₂O and from 15 to 0 cmH₂O for 10 min in steps of 5 cmH₂O.Measurements and results Inflation and deflation V-P curves were constructed from an automated super-syringe that delivers a constant flow of 7 l/min in both inspiratory and expiratory directions. V-P curves were obtained at each level of PEEP without disconnecting the animal from the ventilator. The experimental data were fitted to the sigmoid equation which provided the true inflection point (c), the point of maximal compliance increase (Pmci) reflecting opening/closure and the point of maximal compliance decrease (Pmcd) reflecting end of recruitment/onset of de-recruitment. The sigmoid equation provided an excellent fit. The values of the coefficients of determination were greater than 0.970 (median 0.996, IQR 0.994–0.997 for the 84 determinations). Negative values of Pmci in the deflation limb of the V-P curve were recorded in five pigs, suggesting closure below the volume range studied.Conclusions Inflation and deflation V-P curves at different PEEPs can be fitted by the sigmoid equation. However, further work is needed to investigate the meaning of negative values for Pmci.     

特普他林对油酸性肺损伤鼠肺泡液体清除功能的影响

目的：观察特普他林对油酸致伤大鼠肺损伤后肺泡上皮液体清除能力的影响。方法：采用大鼠油酸型肺损伤模型。大鼠伤后２４小时经气管滴注特普他林（１×１０－ ４ ｍ ｏｌ／Ｌ）溶液５ ｍ ｌ／ｋｇ;１ 小时后检测肺泡内液体清除率（ＡＬＣ）、总肺水量（ＴＬＷ）、肺血管外肺水量（ＥＶＬＷ）和动脉血气参数。结果：大鼠伤后２４ 小时ＡＬＣ降低４９．２％ ,ＴＬＷ 和ＥＶＬＷ 明显增加〔分别由（３．１４±０．１４）ｍ ｌ／ｇ 和（２．２５±０．１１）ｍ ｌ／ｇ 增至（４．０４±０．１３）ｍ ｌ／ｇ和（４．３２±０．１１）ｍ ｌ／ｇ〕,严重的低氧血症〔ＰａＯ２ 为（６．５５±０．２３）ｋＰａ（１ ｋＰａ＝ ７．５ ｍ ｍ Ｈｇ）〕。特普他林组ＡＬＣ较油酸致伤组增高６３．７％ ,ＴＬＷ 和ＥＶＬＷ 显著减少〔分别为（３．３９±０．１６）ｍ ｌ／ｇ 和（２．９４±０．１２）ｍ ｌ／ｇ〕。钠转运特异性抑制剂 阿咪洛利或哇巴因能部分抑制特普他林刺激肺泡内液体清除的作用。结论：特普他林通过上调钠主动转运机能,促进肺水肿液的吸收,从而改善换气功能,对急性肺损伤后肺水肿有一定的治疗作用