幼兔肺冲击伤病理生理特点及其SP-B变化与作用

发布时间：2018-03-28 10:17

  本文选题：肺冲击伤　切入点：幼兔　出处：《第三军医大学》2016年硕士论文

【摘要】：研究背景和目的在现代战争中,随着高爆武器的研发进展及恐怖活动的日益猖獗,爆炸伤的发生率和死亡率不断上升。肺是爆炸伤产生的冲击波的主要靶器官,也是造成伤员死亡的主要原因。其中儿童受到爆炸伤的案例各种媒体也多有报道。婴幼儿的肺等器官尚未完全发育完善,其生物力学特点、损伤机制和伤后病理生理机制与成年的肺等有显著的差异。其中差异最大的要数肺表面活性物质(pulmonary surfactant,PS)的合成与分泌。PS是分布于肺泡内气液表面,主要由肺泡Ⅱ型上皮细胞(alveolar type II epithelial cells,AT-II)合成和分泌的一种脂蛋白复合物。PS的构成中磷脂所占比例约为90%,包括饱和磷脂酰胆碱(DSPC)、磷脂酰甘油(PG)等50余种;肺表面活性蛋白(surfactant protein,SP)所占比例约为10%,目前发现主要包括SP-A、B、C、D四种。在肺泡Ⅱ型细胞中的磷脂循环利用、调控对于外界刺激或感染而引发的炎症反应、参与PS分子膜结构的合成与稳定及抑制肺纤维化等方面具有重要作用。因此爆炸冲击伤所导致的未成熟肺冲击伤伤情特点与救治需求也与成年人有较大差异;尚未完全发育成熟肺的冲击伤研究,有助于深入认识肺冲击伤的机制、病理生理与救治(如表面活性物质在其中的作用)。以往的研究大都是针对成熟肺脏,针对未成熟肺冲击伤的损伤特点、救治及转归的研究报道较少。为此,我们特别建立了一种幼兔重度肺冲击伤动物模型,并与成年兔进行比较,明确未成熟肺冲击伤的疾病特点和救治关键,进一步验证PS在冲击伤过程中的重要作用及相关机制。第一部分:幼兔重度肺冲击伤动物模型的建立研究目的建立稳定的幼兔重度肺冲击伤实验动物模型,为未成熟肺冲击伤机制和肺损伤救治研究提供理想的动物模型。资料和方法致伤驱动压初筛:选取4周龄新西兰白兔16只,随机分为驱动压4.0 MPa组和4.5mpa组,采用bst-Ⅰ型生物激波管,以相应的驱动压力致伤,对比2组肺冲击伤伤情。肺冲击伤伤情特点观察:选取4周龄新西兰白兔48只,随机分为正常对照组(8只)和冲击伤组(40只),依前面研究结果,冲击伤组采用4.5mpa驱动压进行致伤;分别于伤即刻(0h)、2h、4h、6h、12h、24h、48h及72h观测动物生命体征和生理指标、肺大体解剖和光镜病理、测定肺组织含水量等。研究结果致伤驱动压初筛:2组动物均存活,4.0mpa组冲击波超压为(328.16±4.78)kpa,重度肺冲击伤率为12.5%,ais评分(3.38±0.52)分;4.5mpa组冲击波超压为(395.04±11.74)kpa,重度肺冲击伤率为87.5%,ais评分(4.13±0.64)分。肺冲击伤伤情特点观察:致伤动物均存活,伤后即刻出现持续约0.5h的精神萎靡等情况,随后动物呼吸和心率等加快,肺脏出现广泛片状出血和水肿,肺含水量显著增加,多为重度冲击伤,ais评分(3.98±0.55)分,肺光镜病理以肺组织断裂、出血、水肿,伴炎细胞浸润为主。结论利用bst-Ⅰ型生物激波管,采用4.5mpa驱动压可建立稳定的4周龄新西兰白兔重度冲击伤模型,此模型伤情稳定,可用于未成熟肺冲击伤机制和肺损伤救治的实验研究模型。第二部分:幼年兔与成年兔重度肺冲击伤的病理生理特点和其sp-b的变化与作用研究目的比较相同伤情条件下幼年兔与成年兔重度肺冲击伤的疾病变化特点,探讨ps在肺重度冲击伤病理过程中的作用及机制。资料和方法选取成年新西兰白兔40只,4周龄新西兰白兔40只,采用bst-Ⅰ型生物激波管,以4.0mpa和4.5mpa驱动压力致伤,记录冲击波参数,对比2组肺冲击伤伤情,并于伤后0.5h、2h、4h、6h、12h、24h、48h及72h观测动物生命体征和生理指标、肺大体解剖和光镜病理、测定肺组织含水量、血气分析、血常规检测及sp-b含量等。研究结果由BST-Ⅰ型生物激波管在相同驱动压力下所产生的致伤冲击波在压力峰值和持续时间数值较为稳定,幼年组重度肺冲击伤占92.5%,AIS评分(4.12±0.74)分,肺出现面积(40.25±6.78)%;成年兔组重度肺冲击伤占90%,AIS评分(4.03±0.65)分,肺出血面积(38.95±8.33)%,两组间无明显差异(P0.05),伤情较为一致可进行比较。幼年兔组肺含水率(81.32±1.71)%高于成年兔组肺含水率(80.20±1.27)%(P0.01),但其于伤后12h便基本恢复至正常水平,快于成年兔的24h。幼年兔组中性粒细胞百分比于致伤后2-4小时左右达到高峰,并于6-12小时恢复正常;成年兔组则于致伤后4-6小时左右达到高峰,至24-48小时才恢复,且成年兔的峰值明显高于幼年兔,其炎症反应较幼年兔程度更重,持续时间更长。幼年兔SP-B含量(OD值0.3638±0.0546)明显低于成年兔(OD值0.4569±0.0314),且于致伤后迅速降低在4-6小时左右达到最低,下降速度较成年兔快,且恢复较成年兔慢,幼年兔PS合成及分泌功能较成年兔明显不足。尽管成年兔炎症反应及肺水肿程度较重,但由于幼年兔PS水平低下,评价呼吸功能的血样饱和度仍较幼年兔组恢复较快,PS在减少肺泡张力、维持呼吸膜稳定、保障呼吸功能中有着重要作用。结论4.0MPa驱动压力冲击波致伤的成年兔与4.5MPa驱动压力冲击波致伤的幼年兔伤情较为一致,可进行同伤情条件下成年兔与幼年兔冲击伤病理生理变化特点的比较。通过此比较,明确了在重度肺冲击伤中幼年兔较成年兔肺水肿恢复较快、炎症反应较轻;但因PS含量较低,其合成和分泌功能较弱,呼吸功能恢复较慢,证实了PS的不足在伤后肺泡张力恢复、维持肺泡内气液界面稳定、通气和换气功能的恢复中具有重要作用。
[Abstract]:Background and purpose in the modern war, along with the increasingly rampant development of high explosive weapons and terrorist activities, the incidence and mortality of blast injury is increasing. The lung is a major target organ of explosive shock wave produced, but also the main cause of death among children. The wounded by the blast injury cases of various media many of them have been reported. The infant lung has not been fully developed, its biomechanical characteristics, mechanism of injury and injury pathophysiology and adult lung are significantly different. The biggest difference to the number of lung surface active substances (pulmonary, surfactant, PS) and the synthesis and secretion of.PS is distributed in the alveolar gas the surface is mainly composed of type II alveolar epithelial cells (alveolar type II epithelial cells, AT-II) phospholipid synthesis and secretion of a complex lipoprotein.PS in the proportion of about 90%, including full And phosphatidylcholine (DSPC), phosphatidylglycerol (PG) of more than 50 kinds; pulmonary surfactant protein (surfactant, protein, SP) accounted for about 10%, it is mainly including SP-A, B, C, D. Four kinds of phospholipid recycling in alveolar type II cells in the regulation of inflammatory response caused to outside stimulation or infection, and plays an important role in inhibiting pulmonary fibrosis and other aspects involved in the synthesis and stabilization of PS molecular film structure. So the blast injury caused by the immature lung blast injury characteristics and treatment needs are quite different from adults; not yet complete study of impact injury in all mature lung, help for understanding the mechanism of lung impact injury, pathophysiology and treatment (such as surfactant in the role). Most of the previous studies on lung injury characteristics in mature, immature lung blast injury, treatment and research reports to the less. This, we established a rabbit animal model of severe lung blast injury, and compared with the adult rabbit, disease characteristics and treatment key clear immature lung blast injury, to further verify the role of PS in the process of blast injury and the related mechanism. The first part: to establish a rabbit animal model of severe lung blast injury objective to establish a stable rabbit pulmonary blast injury in experimental animal models, to provide an ideal animal model for the mechanism of injury of lung injury and treatment of shock. Materials and methods immature lung injury driving pressure screening: 16 4 week old New Zealand white rabbits were selected and randomly divided into driving pressure of 4 MPa group and 4.5MPa group using bst-, the effects of a biological shock tube, the pressure to drive the corresponding injury, compared 2 groups of pulmonary blast injury. Pulmonary blast injury observed: 48 4 week old New Zealand rabbits were selected and randomly divided into normal control group (8 rats) and impact 浼ょ粍(40鍙，

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