外源性肺泡表面活性物质对重度烧冲复合伤大鼠急性肺损伤的疗效研究

发布时间：2018-01-24 06:26

  本文关键词： 肺泡表面活性物质 烧冲复合伤 肺泡Ⅱ型上皮细胞 肺损伤 大鼠　出处：《天津医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:烧冲复合伤是两种致伤因素(即烧伤和冲击伤)同时或相继叠加于机体而造成的一种复合损伤形式,其死亡率高,病情重,并发症多,救治困难,一直以来是临床亟待需要解决的问题。其中,急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是烧冲复合伤早期死亡的主要原因之一。肺泡表面活性物质(PS)是由肺泡II型上皮细胞分泌的一种脂蛋白,具有使肺泡表面张力降低,维持肺泡稳定性,防止肺水肿,改善氧合的作用。本实验通过建立模拟大鼠烧冲复合伤模型,结合应用外源性肺泡表面活性物质,探讨其对重度烧冲复合伤肺损伤的作用,为临床治疗奠定基础。方法:选取雄性SD大鼠300只,建立重度烧冲复合伤模型,用随机数表法分为假伤组(S)、烧冲复合伤治疗组(T)、烧冲复合伤对照组(C)。每组致伤前0h及伤后6h、24h、48h、72h共5个观察时相点进行观察,使用便携式血气分析仪行血气分析检测;应用大鼠肺功能仪器测定大鼠肺功能;免疫组织化学法检测肺组织髓过氧化物酶的表达的变化;肺组织病理学观察肺组织形态学变化;应用透射电镜观察肺的超微结构;用Western Blot法测定肺组织中肺表面活性物质结合蛋白A含量的时相变化以及caspase3的时相变化。结果:1、血气分析的变化:T组和C组大鼠伤后其氧分压(PaO2)显著下降,两组之间比较,T组显著高于C组(P0.05);T组和C组大鼠伤后其二氧化碳分压(PaCO2)显著升高,两组之间比较,T组显著低于C组(P0.05);T组乳酸含量在各时间点均明显高于C组(P0.05)。2、肺功能的变化:伤后T组大鼠的深吸气量、中心气道阻力、肺顺应性及组织弹性在24h时显著优于C组(P0.05),与S组无统计学差异(P0.05)。3、MPO的变化:T组与C组伤后各时间点均高于S组;C组大鼠肺组织MPO表达升高,浸润程度较多。4、肺组织病理的变化:C组大鼠主要表现为局部肺泡腔破坏、消失,呈实性改变,纤维组织细胞增生,淋巴细胞、浆细胞、中性粒细胞浸润,部分肺泡腔尚存,肺泡上皮细胞脱落,肺泡间隔肿胀、增宽、可见出血,渐进性加重的肺出血及肺水肿,支气管上皮细胞肿胀,上述病变在伤后24h最为严重。T组大鼠大部分肺泡腔结构尚存,淋巴细胞、浆细胞、中性粒细胞浸润、水肿等病理改变程度明显较C组轻。5、透射电镜(TEM)显示:S组大鼠肺组织超微结构正常。T组与C组比较AECⅡ的超微结构发生了系列显著变化。6h T组可见有中性粒细胞浸润,板层小体排空较C组少;24h T组较C组炎性细胞较少,板层小体密度有所增强,体积较均匀,环绕核仁排列;48h T组可见肺泡腔结构,板层小体排空较明显、融合,体积大小不等且不规则,与C组相比较轻,未见巨大板层小体,细胞膜结构有“胞吐”/“胞吸”现象;72h T组板层小体数目略有增加,未见巨大板层小体,体积大小尚均匀,排空略少,重新呈指环状绕核排列。6、肺泡上皮细胞的TUNEL检测显示,6h,T阳性率=0.156,C阳性率=0.410;24h,T阳性率=0.129,C阳性率=0.340;48h,T阳性率=0.105,C阳性率=0.307;72h,T阳性率=0.110,C阳性率=0.316。说明各个时间点T阳性率均小于C阳性率。7、Western Blot法显示,T组和C组SP-A从伤后6h起表达明显低于S组,两组之间比较,T组表达显著高于C组(P0.05)。结论:重度烧冲复合伤大鼠伤后早期即出现急性肺损伤,经气管给予肺泡表面活性物质后,可显著改善大鼠肺泡的通气和换气功能,提高机体氧供,缓解急性肺损伤对全身的损害。
[Abstract]:Objective: burn is two kinds of injury factors (i.e. burn and blast injury) a composite damage form simultaneously or successively superimposed on the body caused by its high mortality rate, severe illness, complications, treatment difficulties, has been a clinical problem urgently to be solved. In the acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) is one of the main causes of early death of burn blast combined injury. Pulmonary surfactant (PS) is a lipoprotein secreted by alveolar type II epithelial cells, with the alveolar surface tension decreased, maintain alveolar stability, prevent lung edema, improve oxygenation function. The simulated rat burn model, application of exogenous pulmonary surfactant combination on severe burn injury of lungs, lay the foundation for clinical treatment. Methods: selected 300 male SD rats, weight set The degree of burn blast combined injury model with randomly divided into sham injury group (S), burn treatment group (T), burn control group (C). Each group before injury and 0h after injury 6h, 24h, 48h, 72h a total of 5 observed time points were observed the use of portable blood gas analyzer, detection and analysis of blood gas; pulmonary function instrument using rat pulmonary function test in rats; myeloperoxidase in lung tissue was detected by immunohistochemical method the expression changes; learn to observe the morphological changes of lung tissue pathology; ultrastructure of lung by transmission electron microscopy; Determination of binding protein A in lung tissue of pulmonary surfactant using Western Blot method and phase change of Caspase3 phase changes. Results: 1. The changes of blood gas analysis: T group and C group rats after injury, the oxygen partial pressure (PaO2) decreased significantly between the two groups, T group was significantly higher than that of C group (P0.05); T group and C group after the second oxidation injury in rats 纰冲垎鍘，

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