密闭舱室大鼠爆炸伤合并失血性休克特点与容量复苏的研究

发布时间：2018-05-04 06:38

本文选题：爆炸伤 + 密闭环境　；参考：《第三军医大学》2010年硕士论文

【摘要】： 现代战争中坦克、装甲车等作战密闭舱室是战时主要的作战装备,也是被打击的重点,而世界范围内以公交车、地铁、公共建筑等人群聚集的密闭场所为主要目标的恐怖袭击发生率也不断增加。因此,无论平时和战时,密闭舱室环境爆炸伤发生率均较高。已经有大量研究报告舱室内爆炸伤重要脏器的损伤特点和机制,研究发现密闭环境内爆炸冲击波传播与开阔地爆炸不同,呈现复杂波特征,表现为冲击波在舱室内反射、叠加,多重压力峰值重叠,超压持续时间长,作用机体后造成的组织脏器挫伤重,肺、脑损伤发生率高。同时,爆炸可造成机体毁损,爆炸产生的弹片和舱体碎片可击中大血管,导致大量失血。因此,密闭环境内爆炸多造成复杂冲击波损伤合并不同程度的失血,重伤员比例高。休克是战创伤最终发展到多脏器功能衰竭必定要经历的阶段,其本质是有效循环血量减少、灌注障碍,炎症介质生成、高水平氧化应激。了解战创伤休克发生、发展的特点和影响因素,开展容量复苏是战创伤救治研究的重要内容。以往虽然有文献报告冲击伤、烧伤和创伤失血性休克的的特点,但对密闭舱室爆炸合并休克少有研究。本项研究采用舱室爆炸实验装置,建立复杂冲击波致伤复合30%失血的大鼠实验模型,了解密闭环境爆炸合并休克的特点,探讨与炎症因子肿瘤坏死因子(TNF)、白介素-6(IL-6)以及氧化应激的关系,检测肺脏中的胱硫醚-γ-裂解酶/硫化氢(CSE/H2S)体系变化,观察肺、脑、肝等脏器损伤改变,在此基础上分别应用晶体、胶体、高渗盐液进行抗休克容量复苏,探讨密闭舱室爆炸伤合并休克的复苏方案以及伤前给予外源性H2S供体对密闭舱室爆炸伤合并失血性休克的调节作用。本研究主要包括以下三个部分,所取得的主要实验结果及结论如下: 第一部分密闭舱室大鼠爆炸伤合并失血性休克特点研究大鼠分为密闭舱室爆炸伤合并失血性休克组,舱外爆炸伤合并失血性休克组和单纯失血性休克组。在与实际装甲车等比例缩小的模拟陆军装甲舱室,将400mg二硝基重氮酚(DDNP)柱状纸质点爆源距离大鼠胸腹部中心11cm瞬时引爆,迅速抽离舱内烟雾,数据采集系统记录舱内压力变化并通过Origin7.0进行滤波和分析处理。然后由股动脉导管匀速放血, 30min放总血量的30%,模拟密闭舱室爆炸伤合并失血性休克。舱外组将大鼠于开阔地致爆炸伤,余实验方法及操作步骤与舱内组相同,单纯失血性休克组作为对照组不做爆炸致伤处理,仅由股动脉放血致休克,统计死亡率,观察各组大鼠血压变化。应用SEDIMENTATION彩色微球沉淀法检测舱内组、舱外组不同时间点肺、肝、脑的血流灌注变化,检测血气、血浆炎症因子变化,观察大鼠肺脑含水率及肺、肝、脑组织的病理变化,检测肺组织过氧化反应水平及肺胱硫醚-γ-裂解酶/硫化氢体系(cystathionine-γ-lysase/hydrogen sulfide, CSE/H2S)体系的变化情况。实验可见舱内组爆炸冲击波为复杂冲击波。与对照组相比,舱内组、舱外组大鼠休克中血压下降快,血压低,而舱内组变化更为明显。与舱外组相比,舱内组大鼠肺、肝、脑组织血流灌注水平低;动脉血氧分压和血氧饱和度低,乳酸浓度高,且氧分压、血氧饱和度开始下降的时间和乳酸浓度增高的时间早;血浆中TNF-α、IL-6浓度升高明显。解剖见舱内组大鼠60%存在颅底出血,肺、肝组织大面积淤血,存在明显的挫伤,而舱外组大鼠几乎不见颅底出血,肺、肝组织仅有少量出血点,无明显挫伤,所有大鼠均无腹腔重要脏器破裂及穿孔,肺脑含水率高于舱外组及对照组。舱内组肺MDA、MPO活性增加幅度大,H2O2浓度高,而SOD活性低(p0.05或p0.01),与此同时肺组织CSE活性和H2S浓度显著降低(p0.05或p0.01)。说明本实验舱内大鼠爆炸伤合并失血性休克,模型稳定,可控性高,可以满足后续实验要求。密闭舱室爆炸伤合并失血性休克死亡率高,血压下降快,幅度大,肺、肝、脑血流灌注水平低,炎症反应明显,且合并多器官复合伤,组织损伤程度重,肺脏氧化应激水平高,肺组织H2S浓度与氧化反应水平密切相关,提示CSE/H2S体系可能参与了肺脏损伤及爆炸伤合并失血性休克过程的调节。第二部分不同类型液体的容量复苏及效果评价对密闭舱室爆炸伤合并失血性休克大鼠进行早期容量复苏。随机将大鼠分为生理盐水组(NS)、羟乙基淀粉胶体组(HS)、7. 5%高渗氯化钠/6%右旋醣酐组(HSD)。观察各组大鼠一般情况,记录平均动脉压变化;在爆炸伤后150min、210min、270min分别活杀8只大鼠,观察大体解剖,血压变化,检测各时相点大鼠肺、肝、脑血流灌注水平,动脉血气指标,血浆炎症因子浓度,计算肺、脑含水率,检测密闭舱室爆炸伤合并失血性休克容量复苏过程中肺组织过氧化反应水平及CSE/H2S浓度变化,以评价不同液体容量复苏对休克血流动力学、炎症反应及组织损伤的改善程度。实验可见:HSD可明显升高血压,增加重要脏器血流灌注,改善血气指标,抑制炎症反应,同时也减轻了肺组织氧化应激损伤(p0.05或p0.01),在一定程度上减弱了密闭舱室爆炸伤合并失血性休克对CSE/H2S体系的影响,容量复苏效果好。第三部分H2S外源性供体NaHS对密闭舱室爆炸伤合并失血性休克的作用大鼠致伤前,由腹腔注射H2S外源性供体,随后静脉输注HSD进行容量复苏,其余检测方法与指标同第二部分。实验结果见早期给予NaHS (10mg/kg, ip)后,大鼠血压变化与对照组差异不明显,但肺、肝、脑组织血流灌注增加,血浆炎症因子水平降低,肺组织过氧化水平较单纯高渗氯化钠/6%右旋醣酐复苏组显著降低(p0.05或P0.01),肺脑含水率下降明显(p0.05或P0.01),治疗效果较单纯应用高渗氯化钠/6%右旋醣酐好。上述研究结果提示 1.密闭舱室爆炸伤合并失血性休克,其发生时间早,血流灌注水平低,炎症反应明显,存在严重的肺、脑水肿和组织损伤,有严重缺氧、酸中毒,进展迅速,代偿能力弱,与舱外组及单纯失血性休克相比,休克休克程度重,预后差,死亡率高。 2.7.5%高渗氯化钠/6%右旋醣酐(HSD)更适合密闭舱室爆炸伤合并失血性休克大鼠容量复苏,可有效升高血压改善肺、肝、脑组织血流灌注,抑制炎症反应,改善氧化应激损伤,保护肺、脑组织。 3.早期给予低剂量H2S(10mg/kg NaHS)可改善肺、肝、脑组织血流灌注,减轻炎症反应及肺组织损伤程度。
[Abstract]:In the modern war, tanks, armored cars and other airtight cabin are the main combat equipment in wartime, and also the focus of the war. The incidence of terrorist attacks in the closed cabin in the world is increasing as the main target of the crowded places, such as buses, subways, public buildings, and so on. The occurrence rate is high. There have been a large number of research reports on the damage characteristics and mechanism of the important organs of the chamber explosion injury. It is found that the explosion shock wave propagation in the closed environment is different from the open explosion, showing the characteristics of complex waves, which shows the reflection, superposition, overlapping of the peak pressure peak, the longer overpressure and the function of the body. At the same time, the incidence of tissue viscera is heavy and the incidence of lung and brain damage is high. At the same time, the explosion can cause damage to the body, the bomb produced by the bomb and the fragments of the hatch can hit the large blood vessels and cause a large amount of blood loss. Therefore, the explosion in the closed environment causes complicated shock wave damage with different range of blood loss, and the proportion of the heavy casualties is high.
Shock is a stage that war trauma eventually develops to multiple organ failure. Its essence is effective circulation reduction, perfusion disorder, inflammatory mediator formation, high level oxidative stress. Understanding the characteristics and influencing factors of the development of war shock, and carrying out capacity recovery is an important content of the research on the treatment of war trauma. There are literature reports on the characteristics of shock, burn, and traumatic hemorrhagic shock, but there are few studies on explosion and shock in closed cabin. In this study, a chamber explosion experimental device was used to establish an experimental model of complex shock induced complex 30% blood loss in rats. The relationship between necrosis factor (TNF), interleukin -6 (IL-6) and oxidative stress was used to detect changes in the cystthioether gamma lyase / hydrogen sulfide (CSE/H2S) system in the lung, and to observe the changes in the lung, brain, liver and other organ damage. On this basis, the shock capacity recovery was carried out with crystal, colloid and hypertonic salt solution, and the explosion injury of the closed cabin combined with shock was discussed. The resuscitation plan and exogenous H2S donor before injury were used to regulate the blast injury and hemorrhagic shock in closed cabin.
This study mainly includes the following three parts. The main results and conclusions are as follows:
Part one characteristics of explosive injury and hemorrhagic shock in closed cabin rats
Rats were divided into closed cabin explosion injury combined with hemorrhagic shock group, extravehicular explosion injury combined with hemorrhagic shock group and simple hemorrhagic shock group. The 400mg two nitro diazonium (DDNP) columnar paper point explosion source was instantaneously detonated from the center of chest and abdomen of rat and quickly extracted from the simulated Army armoured cabin with the actual armoured vehicle. In the cabin smoke, the data collection system records the pressure change in the cabin and filtered and analyzed through Origin7.0. Then the femoral artery catheter is bleeding at a constant speed, and the total blood volume is 30% of the 30min. The explosion injury and hemorrhagic shock are simulated in the closed cabin. The extravehicular group will open the explosion and blast in the open ground, the residual experiment method and the operation steps and the cabin group As the same, the group of simple hemorrhagic shock was not treated as the control group. The blood pressure changes were observed only by the hemorrhagic shock of the femoral artery. The blood pressure changes were observed in each group. The SEDIMENTATION color microsphere precipitation method was used to detect the pulmonary, liver, cerebral blood flow, blood gas and plasma inflammatory factors at different time points of the capsule. The changes in the level of peroxidation and cystathionine- gamma -lysase/hydrogen sulfide (CSE/H2S) system of pulmonary cystathion lysis lyase / hydrogen sulfide (CSE/H2S) system were detected in the lung, liver and brain tissues of the rats. The experimental results showed that the blast shock wave in the capsule was a complex shock wave. Compared with the control group, the cabin was compared with the control group. In the group, the blood pressure of the rats in the extravehicular group was decreased quickly and the blood pressure was low, but the changes in the cabin group were more obvious. Compared with the extravehicular group, the blood flow of the lungs, the liver, the brain tissue was low, the blood oxygen pressure and oxygen saturation were low, the concentration of lactic acid was low, the oxygen pressure, the oxygen saturation began to decline and the time of the lactate concentration increased early. The concentration of TNF- alpha and IL-6 in plasma increased obviously. In the anatomic group, 60% of the rats in the capsule group had skull base bleeding, lung and liver tissue in large area of blood, and there were obvious contusions, but the rats in the outer group had almost no skull base bleeding. There were only a few bleeding points in the lungs and liver tissues, without obvious contusion. All rats had no abdominal major organ rupture and perforation and pulmonary brain water content. The lung MDA, MPO activity increased greatly, the H2O2 concentration was high, and the SOD activity was low (P0.05 or P0.01), while the CSE activity and H2S concentration in the lung tissue decreased significantly (P0.05 or P0.01) in the pulmonary tissue, indicating that the rat explosion injury combined with the hemorrhagic Hugh, the model was stable and high controllability, which could meet the requirements of the follow-up experiment. The mortality of explosion injury combined with hemorrhagic shock is high, blood pressure drops fast, the amplitude is large, lung, liver, cerebral blood flow is low, inflammatory reaction is obvious, and multiple organ complex injury is combined, the degree of tissue injury is heavy, lung oxidative stress level is high, H2S concentration of lung tissue is closely related to the level of oxygenation reaction, suggesting that CSE/H2S system may be involved Regulation of lung injury and explosive injury combined with hemorrhagic shock.
The second part is the capacity recovery and evaluation of different types of fluids.
Early volume recovery was carried out in rats with closed cabin explosion and hemorrhagic shock. Rats were randomly divided into physiological saline group (NS), hydroxyethyl starch colloid group (HS), 7.5% hypertonic sodium chloride /6% dextran group (HSD). The average dynamic pulse pressure changes were recorded in each group, and 150min, 210min, and 270min killed 8 respectively after the explosion injury. Only rats, observe the general anatomy, change of blood pressure, detect the level of lung, liver, cerebral blood flow, arterial blood gas index, plasma inflammatory factor concentration, calculate the lung and brain water content, and detect the changes of lung tissue peroxidation and CSE/H2S concentration in closed cabin explosion injury combined with hemorrhagic shock. The effect of fluid volume resuscitation on shock hemodynamics, inflammatory response and tissue damage can be seen: HSD can obviously increase hypertension, increase blood flow of important organs, improve blood gas index, inhibit inflammatory reaction, and reduce oxidative stress (P0.05 or P0.01) in lung tissue, and to a certain extent weaken the closed cabin explosion. The effect of blast injury combined with hemorrhagic shock on CSE/H2S system is good.
The third part of H2S exogenous donor NaHS was injected with H2S exogenous donor by intraperitoneal injection, followed by intravenous infusion of HSD for volume recovery before injury of rats in closed chamber explosion injury combined with hemorrhagic shock, and the other detection methods and indexes were the same as second parts. The experimental results showed that after early NaHS (10mg/kg, IP), the change of blood pressure and control in rats The difference of the group was not obvious, but the blood flow perfusion in the lung, liver and brain tissue increased, the level of plasma inflammatory factors decreased, the level of lung tissue peroxidation was significantly lower than that of the simple hypertonic sodium chloride /6% dextran resuscitation group (P0.05 or P0.01), and the water content of the lung and brain decreased significantly (P0.05 or P0.01), and the therapeutic effect was better than that of hypertonic sodium chloride /6% dextran.
The results mentioned above suggest
1. the explosive injury of the airtight cabin combined with hemorrhagic shock, its occurrence time is early, the blood flow perfusion level is low, the inflammatory reaction is obvious, there are serious lung, brain edema and tissue damage, there are severe hypoxia, acid poisoning, rapid progress, and weak compensatory ability, and the shock shock degree is heavy, the prognosis is bad, the prognosis is bad, and the mortality is high.
2.7.5% hypertonic sodium chloride /6% dextran (HSD) is more suitable for the volume recovery of rats with airtight compartment explosion and hemorrhagic shock, which can effectively improve hypertension and improve the blood perfusion of the lungs, liver and brain tissue, inhibit the inflammatory reaction, improve the oxidative stress damage, and protect the lung and brain tissue.
3. early administration of low dose H2S (10mg/kg NaHS) can improve the perfusion of lung, liver and brain, reduce inflammation and lung tissue damage.

【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R82

【引证文献】