全肺灌洗对贫铀吸入性肺损伤干预作用的实验研究
发布时间：2018-08-09 14:56
【摘要】：贫铀(depleted uranium,DU)是天然铀提取U235过程中的副产品,是一种具有化学毒性和放射毒性的重金属。因贫铀具有高密度、自发锐性、低造价等特点,以其为原料生产的贫铀武器已广泛应用于军事领域中。当今世界已经有20多个国家和地区公开宣布拥有贫铀武器,并多次在海湾战争,巴尔干战争及伊拉克战争中使用了贫铀弹。贫铀弹爆炸时产生的颗粒散布于自然界中,使空气、水、植被、土壤受到污染,严重损害参战士兵和当地居民身心健康。因此,许多国家都在加大对贫铀武器损伤防护的研究力度。呼吸道吸入是战场上贫铀暴露的最主要途径,研究已发现,贫铀颗粒可通过呼吸道沉积于肺部,导致急慢性肺损伤。减少肺组织贫铀暴露的时间及浓度,是改善贫铀吸入后肺部病变的最根本途径,可惜目前国内外并未找到十分有效的促排剂,仍有待开发新方法以清除肺内贫铀颗粒。本课题建立了贫铀吸入所致的亚急性肺损伤犬模型,并分别于不同时间点对动物模型进行全肺灌洗,了解全肺灌洗对贫铀吸入性肺损伤的干预作用。本课题分为两部分进行,(一)贫铀吸入性亚急性肺损伤模型的建立;(二)全肺灌洗对吸入性肺损伤的干预作用。 第一部分:贫铀吸入性肺损伤犬模型的建立 目的:建立研究用的贫铀吸入性亚急性肺损伤犬模型。 方法:将26犬随机分为空白对照组(n=6)、低剂量组(n=10)、高剂量组(n=10),采用经气管插管将不同浓度的贫铀混悬液分别灌入低剂量组(2mg/kg)和高剂量组(20mg/kg)实验动物左侧肺内,空白对照组仅灌入生理盐水(0.2ml/kg),记录贫铀灌注各组动物的生存时间,观察时间截止为贫铀灌注后30天。在灌注后第30天,对存活犬行肺部CT检查,处死后取肺组织行病理检查。 结果:在30天的观察期内,空白对照组动物无死亡,低剂量组中1只犬在贫铀灌注后22天死亡,其余犬存活均超过30天,高剂量组所有犬均在30天内死亡,存活时间11.2±8.9天。高剂量组与低剂量组和对照组比较,在生存时间上的差异有统计学意义(P0.05),低剂量组与对照组相比,生存时间上的差异无统计学意义(P0.05)。低剂量组肺组织的病理学改变主要为肺泡腔内炎细胞渗出、出血及透明膜形成,肺泡壁毛细血管扩张、充血,肺间质炎细胞浸润,肺CT主要改变为左肺片状渗出影及实变影,腹侧病变重于背侧。 结论:采用贫铀混悬液以2mg/kg剂量行单侧肺灌注所建立的动物模型,适用于进行30天内亚急性贫铀毒性的实验研究。 第二部分:全肺灌洗对贫铀吸入性肺损伤的干预作用 目的:了解全肺灌洗及不同时间点灌洗对贫铀吸入性肺损伤的治疗作用。 方法:以第一部分中的低剂量组(2mg/kg)贫铀使用剂量建立肺损伤模型并作为研究对象,将亚急性肺损伤犬随机分为对照组(n=15),早期灌洗组(n=15),晚期灌洗组(n=15),对早期灌洗组在染毒后第3天、晚期灌洗组在染毒后第14天进行左肺大容量全肺灌洗,灌洗后立即回收,检测早期灌洗组(3天)、晚期灌洗组(14天)动物的支气管肺泡灌洗液(BALF1)中贫铀含量。贫铀灌注30天后,观察各组动物肺部CT影像学改变,同时再次进行支气管肺泡灌洗,检测不同灌洗组动物支气管肺泡灌洗液(BALF2)中细胞因子TNF-α及IL-6含量。贫铀灌注60天后,记录3组动物的生存情况后,处死动物,采用铀荧光发光法测定肺组织铀含量以及细胞因子TNF-α及IL-6含量。 结果:早期灌洗组的生存时间明显高于对照组,晚期灌洗组与对照组比较,生存时间无显著改善。对贫铀吸入性肺损伤犬模型进行全肺灌洗,早期灌洗组肺泡灌洗液(BALF1)中贫铀浓度明显高于晚期灌洗组,差异有统计学意义(P0.05)。30天后,胸部CT分析显示,早期灌洗组与对照组CT评分具有统计学差异(P0.05),晚期灌洗组与对照组比较差异无统计学意义。对肺泡灌洗液(BALF2)中细胞因子TNF-α、IL-6含量检测发现,早期灌洗组中TNF-α、IL-6明显低于对照组,差异有统计学意义(P0.05),晚期灌洗组与对照组之间差异无统计学意义(P0.05)。60天后处死动物检测发现,早期灌洗组肺组织的贫铀含量、肺组织匀浆上清中TNF-α、IL-6均低于对照组,差异有统计学意义(P0.05),晚期灌洗组肺组织的铀含量、TNF-α、IL-6与对照组之间比较无统计学差异(P0.05)。 结论:早期和晚期行全肺灌洗均能洗出一定数量的贫铀颗粒,但早期灌洗能显著延长贫铀吸入性肺损伤动物的生存期、改善肺部影像学变化及减轻肺部炎症反应。
[Abstract]:Depleted uranium (DU) is a by-product in the process of extracting U235 from natural uranium. It is a heavy metal with chemical and radiological toxicity. Because of the characteristics of high density, spontaneous and low cost of depleted uranium, it has been widely used in Yu Jun's field. There are already more than 20 countries and regions in the world today. A public announcement of the possession of depleted uranium weapons, and the use of depleted uranium ammunition in the Gulf War, the Balkan War and the Iraq war. The particles produced by the depleted uranium bomb are scattered in the natural world, causing air, water, vegetation, and soil to be polluted, and seriously damaging the physical and mental health of the soldiers and the local residents. Respiratory tract inhalation is the most important way for the exposure of depleted uranium in the battlefield. It has been found that depleted uranium particles can be deposited in the lungs through the respiratory tract, leading to acute and chronic lung injury. Reducing the time and concentration of depleted uranium exposure in the lung tissue is the most fundamental way to improve the lung disease after the inhalation of depleted uranium. We have not found a very effective promoter and still need to develop a new method to remove the lung depleted uranium particles. This subject has established a subacute lung injury dog model caused by inhalation of depleted uranium, and the whole lung lavage is carried out at different time points to understand the intervention effect of whole lung lavage on depleted uranium inhalation lung injury. The subject is divided into two Part one is to establish a model of depleted uranium inhalation subacute lung injury. (two) the intervention effect of whole lung lavage on inhalation lung injury.
Part I: establishment of a model of depleted uranium inhalation lung injury in dogs
Objective: to establish a model of depleted uranium inhalation subacute lung injury in dogs.
Methods: 26 dogs were randomly divided into blank control group (n=6), low dose group (n=10) and high dose group (n=10). The different concentration of depleted uranium suspension was injected into the left lung of the low dose group (2mg/kg) and the high dose group (20mg/kg), and the empty white control group was only injected into the normal saline (0.2ml/kg), and the animals were injected with depleted uranium in each group. The survival time and the observation time were 30 days after the injection of depleted uranium. After thirtieth days of perfusion, the lungs of the surviving dogs were examined by CT.
Results: in the 30 day observation period, there was no death in the blank control group. In the low dose group, 1 dogs died after 22 days of depleted uranium perfusion. The remaining dogs survived more than 30 days. All dogs in the high dose group died within 30 days and the survival time was 11.2 8.9 days. The difference in the survival time between the high dose group and the low dose group was statistically significant compared with the control group. P0.05, there was no significant difference in the survival time between the low dose group and the control group (P0.05). The pathological changes of lung tissue in the low dose group were mainly alveolar inflammatory cells exudation, bleeding and transparent membrane formation, pulmonary alveolar capillary dilatation, congestion, pulmonary interstitial inflammatory cells infiltration, and lung CT mainly changed to left lung flaky exudation. In real change, the ventral lesion is heavier than the dorsal side.
Conclusion: the animal model established by single dose lung perfusion with dose of 2mg/kg depleted uranium is suitable for the experimental study of subacute toxicity of uranium in 30 days.
The second part: the intervention effect of whole lung lavage on depleted uranium inhalation lung injury.
Objective: To investigate the therapeutic effects of lavage and lavage at different time points on inhaled lung injury induced by depleted uranium.
Methods: in the first part of the low dose group (2mg/kg), the lung injury model was established and used as the research object. The subacute lung injury dogs were randomly divided into control group (n=15), early lavage group (n=15) and late lavage group (n=15). The early lavage group was exposed to the early lavage group for third days, and the late lavage group took the left lung capacity after fourteenth days of exposure. All lung lavage and reclaim immediately after lavage, the content of depleted uranium in bronchoalveolar lavage fluid (BALF1) in the early lavage group (3 days) and the bronchoalveolar lavage fluid (14 days) in the late lavage group (14 days). After 30 days after the infusion of depleted uranium, the CT imaging changes of the lungs were observed, and bronchoalveolar lavage was carried out again, and the bronchoalveolar lavage fluid (BAL) in the different lavage groups was detected (BAL The content of cytokine TNF- alpha and IL-6 in F2. After 60 days of infusion of depleted uranium, the survival of 3 groups of animals were recorded and animals were killed. Uranium content in lung tissue and the content of cytokines TNF- A and IL-6 were measured by uranium fluorescence method.
Results: the survival time of the early lavage group was significantly higher than that in the control group. There was no significant improvement in the survival time between the late lavage group and the control group. The whole lung lavage was performed on the canine model of depleted uranium inhalation lung injury, and the concentration of depleted uranium in the alveolar lavage fluid (BALF1) in the early lavage group was significantly higher than that in the late stage lavage group (P0.05).30 days, The chest CT analysis showed that the CT score of the early lavage group and the control group had statistical difference (P0.05), and there was no significant difference between the late lavage group and the control group. The detection of the cytokines TNF- A and IL-6 in the alveolar lavage fluid (BALF2) showed that the TNF- alpha and IL-6 in the early lavage group were significantly lower than those in the control group (P0.05), and the difference was statistically significant (P0.05), late and late. There was no significant difference between the period lavage group and the control group (P0.05).60 days after the death of the animals found that the content of depleted uranium in lung tissue in the early lavage group, TNF- alpha in the lung homogenate supernatant and IL-6 were lower than those in the control group (P0.05). The uranium content of lung tissue in the late lavage group, TNF- a, IL-6 and the control group were no more unified. Study difference (P0.05).
Conclusion: early and late full lung lavage can wash out a certain amount of depleted uranium particles, but early lavage can significantly prolong the survival period of the animals with depleted lung injury, improve the pulmonary imaging changes and reduce the pulmonary inflammatory response.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332;R563
[Abstract]:Depleted uranium (DU) is a by-product in the process of extracting U235 from natural uranium. It is a heavy metal with chemical and radiological toxicity. Because of the characteristics of high density, spontaneous and low cost of depleted uranium, it has been widely used in Yu Jun's field. There are already more than 20 countries and regions in the world today. A public announcement of the possession of depleted uranium weapons, and the use of depleted uranium ammunition in the Gulf War, the Balkan War and the Iraq war. The particles produced by the depleted uranium bomb are scattered in the natural world, causing air, water, vegetation, and soil to be polluted, and seriously damaging the physical and mental health of the soldiers and the local residents. Respiratory tract inhalation is the most important way for the exposure of depleted uranium in the battlefield. It has been found that depleted uranium particles can be deposited in the lungs through the respiratory tract, leading to acute and chronic lung injury. Reducing the time and concentration of depleted uranium exposure in the lung tissue is the most fundamental way to improve the lung disease after the inhalation of depleted uranium. We have not found a very effective promoter and still need to develop a new method to remove the lung depleted uranium particles. This subject has established a subacute lung injury dog model caused by inhalation of depleted uranium, and the whole lung lavage is carried out at different time points to understand the intervention effect of whole lung lavage on depleted uranium inhalation lung injury. The subject is divided into two Part one is to establish a model of depleted uranium inhalation subacute lung injury. (two) the intervention effect of whole lung lavage on inhalation lung injury.
Part I: establishment of a model of depleted uranium inhalation lung injury in dogs
Objective: to establish a model of depleted uranium inhalation subacute lung injury in dogs.
Methods: 26 dogs were randomly divided into blank control group (n=6), low dose group (n=10) and high dose group (n=10). The different concentration of depleted uranium suspension was injected into the left lung of the low dose group (2mg/kg) and the high dose group (20mg/kg), and the empty white control group was only injected into the normal saline (0.2ml/kg), and the animals were injected with depleted uranium in each group. The survival time and the observation time were 30 days after the injection of depleted uranium. After thirtieth days of perfusion, the lungs of the surviving dogs were examined by CT.
Results: in the 30 day observation period, there was no death in the blank control group. In the low dose group, 1 dogs died after 22 days of depleted uranium perfusion. The remaining dogs survived more than 30 days. All dogs in the high dose group died within 30 days and the survival time was 11.2 8.9 days. The difference in the survival time between the high dose group and the low dose group was statistically significant compared with the control group. P0.05, there was no significant difference in the survival time between the low dose group and the control group (P0.05). The pathological changes of lung tissue in the low dose group were mainly alveolar inflammatory cells exudation, bleeding and transparent membrane formation, pulmonary alveolar capillary dilatation, congestion, pulmonary interstitial inflammatory cells infiltration, and lung CT mainly changed to left lung flaky exudation. In real change, the ventral lesion is heavier than the dorsal side.
Conclusion: the animal model established by single dose lung perfusion with dose of 2mg/kg depleted uranium is suitable for the experimental study of subacute toxicity of uranium in 30 days.
The second part: the intervention effect of whole lung lavage on depleted uranium inhalation lung injury.
Objective: To investigate the therapeutic effects of lavage and lavage at different time points on inhaled lung injury induced by depleted uranium.
Methods: in the first part of the low dose group (2mg/kg), the lung injury model was established and used as the research object. The subacute lung injury dogs were randomly divided into control group (n=15), early lavage group (n=15) and late lavage group (n=15). The early lavage group was exposed to the early lavage group for third days, and the late lavage group took the left lung capacity after fourteenth days of exposure. All lung lavage and reclaim immediately after lavage, the content of depleted uranium in bronchoalveolar lavage fluid (BALF1) in the early lavage group (3 days) and the bronchoalveolar lavage fluid (14 days) in the late lavage group (14 days). After 30 days after the infusion of depleted uranium, the CT imaging changes of the lungs were observed, and bronchoalveolar lavage was carried out again, and the bronchoalveolar lavage fluid (BAL) in the different lavage groups was detected (BAL The content of cytokine TNF- alpha and IL-6 in F2. After 60 days of infusion of depleted uranium, the survival of 3 groups of animals were recorded and animals were killed. Uranium content in lung tissue and the content of cytokines TNF- A and IL-6 were measured by uranium fluorescence method.
Results: the survival time of the early lavage group was significantly higher than that in the control group. There was no significant improvement in the survival time between the late lavage group and the control group. The whole lung lavage was performed on the canine model of depleted uranium inhalation lung injury, and the concentration of depleted uranium in the alveolar lavage fluid (BALF1) in the early lavage group was significantly higher than that in the late stage lavage group (P0.05).30 days, The chest CT analysis showed that the CT score of the early lavage group and the control group had statistical difference (P0.05), and there was no significant difference between the late lavage group and the control group. The detection of the cytokines TNF- A and IL-6 in the alveolar lavage fluid (BALF2) showed that the TNF- alpha and IL-6 in the early lavage group were significantly lower than those in the control group (P0.05), and the difference was statistically significant (P0.05), late and late. There was no significant difference between the period lavage group and the control group (P0.05).60 days after the death of the animals found that the content of depleted uranium in lung tissue in the early lavage group, TNF- alpha in the lung homogenate supernatant and IL-6 were lower than those in the control group (P0.05). The uranium content of lung tissue in the late lavage group, TNF- a, IL-6 and the control group were no more unified. Study difference (P0.05).
Conclusion: early and late full lung lavage can wash out a certain amount of depleted uranium particles, but early lavage can significantly prolong the survival period of the animals with depleted lung injury, improve the pulmonary imaging changes and reduce the pulmonary inflammatory response.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332;R563
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