急性肺损伤血栓素A2受体、受体mRNA的变化及拮抗剂酚红对它们的影响

目的研究急性肺损伤（ＡＬＩ）肺组织特异性膜受体（ＴＸＡ２Ｒ）的变化及受体拮抗剂酚红对它们的影响，从分子水平阐明血栓素Ａ２（ＴＸＡ２）在ＡＬＩ中的作用机制。方法采用大鼠油酸肺损伤模型，分析伤后６小时肺组织ＴＸＡ２Ｒ、ＴＸＡ２ＲｍＲＮＡ表达的变化以及酚红（５０ｍｇ／ｋｇ、５ｍｇ／ｋｇ）对它们的影响。结果油酸肺损伤后肺组织ＴＸＡ２Ｒ结合容量明显“降低”，其ｍＲＮＡ的转录显著升高。酚红的应用使ＴＸＡ２Ｒ结合容量明显“降低”，并能抑制油酸肺损伤ＴＸＡ２ＲｍＲＮＡ转录的增高。酚红能显著降低肺体指数（ＬＢＩ）、肺含水率（ＲＬＷ），改善动脉血氧分压（ＰａＯ２），减轻肺组织损伤程度。结论ＴＸＡ２在ＡＬＩ的病理过程中具有重要作用。体内试验证明酚红能有效地调节ＴＸＡ２Ｒ及其ｍＲＮＡ的表达并对ＡＬＩ的发生有防护作用     

急性肺损伤大鼠白细胞变形性变化及山莨菪碱影响

目的 探讨多形核白细胞（ＰＭＮ）变形性变化在大鼠内毒素性急性肺损伤（ＡＬＩ）中的作用机制及山莨菪碱对ＰＭＮ变形性变化的影响。方法 ４４只大鼠通过静脉注射内毒素（５ｍｇ／ｋｇ）复制大鼠ＡＬＩ模型，每组分为：（１）内毒素１小时组（８只）；（２）内毒素４小时组（８只）；（３）内毒素６小时组（８只）；（４）山莨菪碱治疗组（８只），注射内毒素后，立即静脉注射山莨菪碱５ｍｇ／ｋｇ；（５）正常对照组（１２只），     

允许性高碳酸血症对急性肺损伤绵羊肺力学及血流动力？…

目的 探讨允许性高碳酸血症（ＰＨＣ）对急性肺损伤（ＡＬＩ）绵羊肺力学及血流动力学的影响。方法 观察不同潮气量（ＶＴ）时，１８只ＡＬＩ绵羊肺气体交换、肺力学和血流动力学的改变。结果 当ＶＴ从１６ｍｌ／ｋｇ降至４～７ｍｌ／ｋｇ时，绵羊均出现ＰＨＣ，动脉血氧分压、氧饱和度和混合静脉血氧饱和度显降低（Ｐ〈０．０５）。ＰＨＣ时气道压力显降低（Ｐ〈０．０５），气道阻力明显增高；体循环和肺循环阻力指数、左心     

小剂量甲氨蝶呤对RA患者血浆TNFαIL-6水平影响的研究

目的 探讨小剂量甲氨蝶呤（ＭＴＸ）对ＲＡ患者血浆ＴＮＦα、ＩＬ－６水平的影响。方法 用放射免疫分析（ＲＩＡ）法研究了３０例ＲＡ患者ＭＴＸ（１０ｍｇ／Ｗ）治疗前后血浆ＴＮＦα、ＩＬ－６水平的变化。结果 ＭＴＸ治疗６周后血浆ＴＮＦα、ＩＬ－６水平明显降低，以后进一步降低（Ｐ〈０．０１）。结论 ＭＴＸ能有效地降低ＲＡ患者血浆ＴＮＦα、ＩＬ－６水平，诱导病情缓解。     

容许性高碳酸血症对急性肺损伤动物心肺功能影响的观察

观察不同水平的容许性高碳酸血症（ＰＨＣ）对油酸型急性肺损伤（ＡＬＩ）模型的心肺功能影响。方法复制猪ＡＬＩ模型，四腔热稀释漂浮导管监测血液动力学及不同潮气量致不同程度的ＰＨＣ。结果ＡＬＩ导致明显的心肺功能恶化。呼气末正压可改善部分病理生理指标，但吸气末平台压（Ｐｅｅ）明显升高。潮气量（ＶＴ）降至７．７±０．３ｍｌ／ｋｇ、动脉血二氧化碳分压（ＰａＣＯ２）升至９．４４±１．２７ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ）时，心输出量明显改善而其它心肺功能无明显改变。ＶＴ降至６．１±０．６ｍｌ／ｋｇ、Ｐａ－ＣＯ２为１２．１±１．０５ｋＰａ时，虽气道峰压下降，但Ｐｅｅ未见降低且其它心肺指标恶化。结论合适的低潮气量致一定程度的ＰＨＣ是较为安全的通气方式。     

美吡哒加小剂量阿斯匹林治疗糖尿病28例疗效分析

本文观察了２８例Ⅱ型糖尿病并血管病变患者的血小板功能及血浆ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ（Ｔ／６－ｋ）比值；比较了美吡哒与美吡哒加小剂量阿斯匹林（ＡＳＡ）对它们的影响。结果显示该组患者血小板聚集功能亢进，血浆Ｔ／６－ｋ的比值显著升高。单用美吡哒可显著降低血糖，但未发现抗血小板作用。每日加０．５ｍｇ／ｋｇ的ＡＳＡ可选择性抑制血小板功能，纠正血浆Ｔ／６－ｋ的失衡。     

氢化可的松和氟美松对人红细胞膜胰岛素受体的影响

实验结果发现，口服氢化可的松（１．２５ｍｇ／ｋｇ）和氟美松（３７．５μｇ／ｋｇ）后红细胞膜胰岛素受体的最大特异性结合率（Ｂ／Ｔ）显著下降，血浆胰岛素浓度显著升高，而血糖无明显变化。Ｓｃａｔｃｈａｒｄ图显示结合率的改变主要不是受体亲和力和数目变化所致。体外实验结果表明两者对红细胞膜胰岛素受体的结合无显著影响。提示两者对胰岛素受体的影响是多层次的，包括胰岛素的分泌和受体与胰岛素的结合。     

血管紧张素Ⅱ型受体主其介导的生物学作用

血管紧张素Ⅱ（ＡｎｇⅡ）的生理效应是通过与不同组织浆膜上的受体结合后发挥的,其受体具有多中类型。目前已知ＡｎｇⅡ的主要作用是通过一型受体（ＡＴ１）介导的,包括调节肺、肝、脑和肾脏的功能,产生血管收缩,促进细胞生长和增殖,释放激素、调节血容量等效应。刺激二型受体（ＡＴ２）能够拮抗ＡＴ１受体的效应。ＡＴ２受体主要存在于胚胎组织及成人的脑组织、肾上腺髓质、子宫和卵巢。其基因定位于Ｘ染色体上。主要生物效应     

血小板聚集导致微栓塞在腔隙性脑梗塞发病中的作用

测定了１６２例腔隙性梗塞（ＬＩ）患者的血小板聚集率（ＰＡ），并测定了其中３０例高聚患者的血小板内ＴＸＡ２和ｃＡＭＰ含量及例ＬＩ患者的红细胞变形指数（ＤＩ），发现Ｌ的血小板最大聚集率（ＭＡＲ）、ＴＸＡ２、ｃＡＭＰ含量变化及ＤＩ与健康对照组有显著差异，同时对３０例高聚ＬＩ患者进行了颈动脉系统颅外段Ｂ型多普勒超声断层扫描，发现动脉硬化阳性率７３．３％，表明血小板聚集率增高导致的微栓塞是ＬＩ的重要原因。     

肝损伤小鼠肝组织氧化／抗氧化平衡的变化及其与TXA2／PGI2？…

目的：探讨氧自由基（ＯＦＲ）及ＴＸＡ２－ＰＧＩ２在实验性肝损伤中的作用。方法：检测肝损伤小鼠肝组织过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）含量以及血浆ＴＸＡ和ＰＧＩ２浓度。结果：与对照组比较肝损伤小鼠ＬＰＯ明显升高、ＳＯＤ明显降低，当归可逆转ＬＰＯ和ＳＯＤ的变化；肝损伤小鼠血浆ＴＸＢ２高于对照组，其浓度与肝细胞ＬＰＯ含量呈正相关（ｒ＝０．９５，Ｐ〈０．０１）。结论：ＯＦＲ与ＴＸＡ２／ＰＧＩ２     

The study of thromboxane A2 and prostacyclin in oleic acid-induced lung injury in dogs

Acute lung injury was produced by intravenous injection of oleic acid. After oleic acid injection, PaO2 was decreased, dogs were involved in respiratory distress. Histological examination indicated aggregation of leukocytes in microvasculature, interstitial and intraalveolar pulmonary edema and congestion in the lung. Using radioimmunoassay technique, changes in arterial and venous plasma levels of stable metabolite of thromboxane A2 (TXA2), thromboxane B2 (TXB2) have been observed. After oleic acid administration, plasma 6-keto-PGF1alpha level was markedly elevated with two peaks. 6-keto-PGF1alpha level in arteries was higher in concentration than in veins. It was suggested that the lung might synthesis a great quantity of prostacyclin entering the systemic circulation. TXB2 was markedly elevated in plasma, which was more in veins than in arteries. A significant arteriovenous difference suggests that there might be extrapulmonary sources contributing to the elevation of plasma TXB2 in oleic acid induced lung injury in dogs. After treatment with large dose of anisodamine (654-2), platelets and leukocytes aggregation could be inhibited as well as the synthesis of TXA2 and prostacyclin. 654-2 might play a role of cyclo-oxygenase inhibitor. It was suggested that 654-2 reduce synthesis of the precursors of TXA2 and prostacyclin, reduce pulmonary edema and might be a therapeutical effect to lung injury.     

急性肺损伤时大鼠肺组织connexin32 mRNA表达的变化

目的观察急性肺损伤不同时段大鼠肺组织中缝隙连接蛋白connexin32 mRNA（Cx32 mRNA）表达的变化,探讨缝隙连接与急性肺损伤发生、发展及修复的关系。方法采用油酸（0.25ml/kg）经大鼠尾静脉缓慢注入复制急性肺损伤模型,分别于注射油酸后1、5、12、24和48小时取出肺脏,用原位杂交方法评价Cx32 mRNA的表达情况。结果原位杂交显示Cx32 mRNA的表达主要定位于细胞质中。Cx32 mRNA在正常组及损伤后1、5、12、24、48小时组的平均阳性表达率分别为13.95%、5.53%、4.83%、5.27%、6.80%、8.92%。正常对照组Cx32 mRNA阳性细胞率较损伤各组高（P〈0.001）,急性肺损伤后12小时内Cx32 mRNA阳性细胞率迅速下降（P〈0.001）,损伤后第12小时到第48小时Cx32 mRNA阳性细胞率缓慢上升（P〈0.05）。结论 Cx32 mRNA表达的改变可能与急性肺损伤的发生、发展及其修复有密切的关系。     

Cyclooxygenase metabolites contribute to oleic acid-induced lung edema by a pressure effect

We investigated the role that lung-derived arachidonic acid metabolites play in the acute changes in pulmonary hemodynamics, airway function, and lung fluid balance following oleic acid-induced injury in the isolated blood free perfused lung. A bolus injection of oleic acid (OA) emulsion (12 mg) into the pulmonary artery caused a rapid increase in pulmonary arterial pressure, inspiratory pressure, and weight gain. These pathophysiologic changes were not due to emboli per se, but were correlated with release of the vaso- and broncho-constrictive prostanoids, thromboxane A2 (measured as thromboxane B2) and prostaglandin F2 alpha. The leukotrienes (C4, D4, and E4) and prostacyclin (measured as 6 keto-prostaglandin F1 alpha) were not released by OA injury. Ibuprofen, a cyclooxygenase inhibitor, blocked the release of the vasoconstrictive prostanoids and also attenuated the rise in pressures and the development of edema indicating an important functional role for the prostanoids in the fluid imbalance. Ibuprofen also attenuated the increase in bronchoalveolar lavage protein but the protein leak was not completely prevented, suggesting that OA-induced increases in protein permeability occurred independently of prostanoid or leukotriene action. These data indicate that OA-induced edema formation was greatly amplified by arachidonic acid mediated pressure increases.     

Effects of N-acetylcysteine on oxidant-antioxidant balance in oleic acid-induced lung injury

The antioxidant and anti-inflammatory properties of N-acetylcysteine has been documented in many experimental lung injury models. Because intravenous injection of oleic acid induces histopathologic changes similar to those seen in human acute lung injury or acute respiratory distress syndrome, the authors evaluated the effects of N-acetylcysteine (NAC) on oxidative stress and lung damage in an oleic acid (OA)-induced lung injury model. Thirty-five rats were divided into 5 groups as sham, NAC, OA, pre-OA-NAC, and post-OA-NAC. Lung damage was induced by intravenous administration of oleic acid. Pre-OA-NACgroup received intravenous (IV) N-acetylcysteine 15 minutes before oleic acid infusion and post-OA-NAC group received IV N-acetylcysteine 2 hours after oleic acid infusion. In both of the N-acetylcysteine treatment groups, blood and tissue samples were collected 4 hours after oleic acid infusion, independent from the time of N-acetylcysteine infusion. In other groups, blood and tissue samples were collected 4 hours after ethanol, NAC, or OA infusions. Serum myeloperoxidase activity, total antioxidant capacity, malondialdehyde levels, and lung tissue Na+ - K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The administration of N-acetylcysteine significantly restored Na+ - K+ ATPase activity and total antioxidant capacity levels and ameliorated lung architecture. N-acetylcysteine has been shown to have some attenuating effects in experimental animal studies. However, further investigations are necessary to suggest N-acetylcysteine as a treatment agent in critically ill patients with lung injury.     

骨髓间充质干细胞移植调节TNF-α和IL-10浓度减轻十八稀酸诱导的大鼠急性肺损伤

目的:探讨骨髓间充质干细胞(MSCs)移植对十八稀酸诱导大鼠急性肺损伤(ALI)的影响。方法:颈静脉内注射十八稀酸(10μL/kg)建立大鼠ALI模型,实验组给于大鼠骨髓间充质干细胞悬浊液,对照组给于同等剂量磷酸缓冲(PBS)溶液。在不同时间点(8 h,24 h和48 h)处死大鼠,评价肺病理学特点、肺组织和血浆中肿瘤坏死因子-α(TNF-α)和白介素-10(IL-10)的浓度。结果:MSCs移植在不同时间点上均能显著性降低肺组织内中性粒细胞浸润,抑制肺组织和血浆内TNF-α浓度,同时升高IL-10浓度。结论:骨髓间充质干细胞移植,显著降低肺组织和血浆中TNF-α浓度时升高IL-10浓度,减低十八稀酸所致大鼠肺损伤,其可成为ALI和急性呼吸窘迫综合征(ARDS)一种潜在的细胞治疗方法。     

2种用油酸诱导的幼猪急性肺损伤模型血流动力学变化的对比分析

目的:对比以"近似二次打击"的方法和传统方法构建的油酸诱导的幼猪急性肺损伤模型的血流动力学差异。方法:外科操作稳定30 min后,12只幼猪随机分为传统诱导组(T组)和"近似二次打击"诱导组(H组),T组油酸连续经右心耳注射,H组采取近似于"近似二次打击"的方法,分2阶段间隔1 h经右心耳连续注射油酸。于各时间点记录血流动力学指标,并取动脉血行血气分析检查。注射油酸后3 h处死实验动物。结果:T组有2只幼猪死于油酸应用后发生的急剧的血压下降;T组血流动力学改变较H组剧烈,尤其以油酸注射后的5~30 min最为剧烈。实验过程中2组左心房压无显著变化,油酸注射后肺动脉压力显著升高。结论:以油酸按"近似二次打击"法构建的急性肺损伤模型的血流动力学较传统法稳定,2种方法构建的模型均能达到急性肺损伤模型的标准。     

气体信号分子硫化氢在油酸致大鼠急性肺损伤中的作用

目的:探讨胱硫脒-γ-裂解酶(cystathionine-γ-lyase,CSE)/硫化氢(hydrogen sulfide,H2S)系统在急性肺损伤(acute lunginjury,ALI)中的作用。方法:尾静脉注射油酸(oleic acid,OA)制备大鼠ALI模型为OA组,对照组注射等量生理盐水,注射OA前给予硫氢化钠(NaHS)(14μmol/kg)作为NaHS+OA组,单纯给予NaHS(14μmol/kg)作为NaHS组,分别测定血浆及肺组织H2S生成量、CSE活性、3-巯基丙酮酸转硫酶(3-mercaptopyruvate sulfurtransferase,MPST)活性、肺组织及血浆中丙二醛(MDA)、共轭二烯(Diene)键含量;并对肺部病变进行评定。结果:与对照组比较,OA组肺组织CSE、MPST活性及H2S浓度呈现下降趋势(P<0.01),血浆H2S浓度升高(P<0.01),血浆及肺组织MDA及Diene键含量升高(P<0.01);与OA组比较,NaHS+OA组血浆及肺组织MDA和Diene键含量明显下降(P<0.01)。结论:内源性CSE/H2S系统参与了OA致大鼠ALI的病理生理过程;给予外源性H2S可以减轻ALI时肺脏脂质过氧化损害。     

Physiologic, biochemical, and imaging characterization of acute lung injury in mice

RATIONALE: Most models of acute lung injury in mice have yet to be fully characterized. OBJECTIVES: To directly compare and contrast endotoxin and oleic acid models of acute lung injury in mice in terms of their physiologic, biochemical, histopathologic, and imaging manifestations. METHODS: Survival studies, lung weights, x-ray computed tomographic scanning, light and electron microscopy, bronchoalveolar lavage, lung uptake of ((18)F)fluorodeoxyglucose, tissue myeloperoxidase, arterial blood gases, mean arterial pressure, and lung tissue prostanoids were measured in separate groups of C57Bl/6 mice (normal animals, endotoxin only [20 microg/g], oleic acid only [0.15 microl/g], or endotoxin + oleic acid). RESULTS: Endotoxin alone caused only mild pulmonary neutrophilic inflammation with little functional or structural damage to the alveolar architecture. In contrast, oleic acid caused severe alveolar damage with the development of alveolar edema of the increased-permeability type with associated abnormalities in gas exchange. When given together, endotoxin and oleic acid acted synergistically to increase pulmonary edema and to worsen gas exchange and hemodynamics, thereby increasing mortality. This synergism was significantly attenuated by the prior administration of the endotoxin antagonist E5564 (eritoran). CONCLUSIONS: Under the conditions of these studies, only mice exposed to oleic acid showed both structural and functional characteristics of acute lung injury. Nevertheless, endotoxin had potent synergistic physiologic effects that increased mortality. Overall, these models, which can be translated to genetically altered mice, are amenable to study with state-of-the-art imaging techniques, and with experimental interventions that can probe the underlying mechanisms of injury.     

Polymorphonuclear leukocyte participation in acute oleic-acid-induced lung injury

The purpose of this study was twofold: (1) to analyze the cellular components of bronchoalveolar lavage fluid throughout the development of oleic-acid-induced lung injury in the rat and (2) to investigate the role of polymorphonuclear leukocytes (PMN) in the pathogenesis of this disease. Animals were killed and lavaged at various times after a single intravenously administered injection of oleic acid. The results demonstrate that a significant influx of inflammatory cells appear in the lavage fluid as early as 4 h after the administration of oleic acid. The PMN are the first cells to appear, and significant levels persist through Day 5 after injection. There is a transient yet significant influx of lymphocytes between 3 and 7 days after treatment. Rats treated with oleic acid displayed significant increases in lung vascular permeability over control animals at 1 and 4 h after injection. Depletion of PMN by anti-PMN serum significantly decreased the permeability changes induced by oleic acid. Treatment of oleic-acid-injected animals with catalase, superoxide dismutase, or dimethyl sulfoxide failed to inhibit lung permeability changes induced in this model.