全肺灌洗對(duì)貧鈾吸入性肺損傷干預(yù)作用的實(shí)驗(yàn)研究
發(fā)布時(shí)間：2018-08-09 14:56
【摘要】：貧鈾(depleted uranium,DU)是天然鈾提取U235過(guò)程中的副產(chǎn)品,是一種具有化學(xué)毒性和放射毒性的重金屬。因貧鈾具有高密度、自發(fā)銳性、低造價(jià)等特點(diǎn),以其為原料生產(chǎn)的貧鈾武器已廣泛應(yīng)用于軍事領(lǐng)域中。當(dāng)今世界已經(jīng)有20多個(gè)國(guó)家和地區(qū)公開(kāi)宣布擁有貧鈾武器,并多次在海灣戰(zhàn)爭(zhēng),巴爾干戰(zhàn)爭(zhēng)及伊拉克戰(zhàn)爭(zhēng)中使用了貧鈾彈。貧鈾彈爆炸時(shí)產(chǎn)生的顆粒散布于自然界中,使空氣、水、植被、土壤受到污染,嚴(yán)重?fù)p害參戰(zhàn)士兵和當(dāng)?shù)鼐用裆硇慕】�。因�?許多國(guó)家都在加大對(duì)貧鈾武器損傷防護(hù)的研究力度。呼吸道吸入是戰(zhàn)場(chǎng)上貧鈾暴露的最主要途徑,研究已發(fā)現(xiàn),貧鈾顆�？赏ㄟ^(guò)呼吸道沉積于肺部,導(dǎo)致急慢性肺損傷。減少肺組織貧鈾暴露的時(shí)間及濃度,是改善貧鈾吸入后肺部病變的最根本途徑,可惜目前國(guó)內(nèi)外并未找到十分有效的促排劑,仍有待開(kāi)發(fā)新方法以清除肺內(nèi)貧鈾顆粒。本課題建立了貧鈾吸入所致的亞急性肺損傷犬模型,并分別于不同時(shí)間點(diǎn)對(duì)動(dòng)物模型進(jìn)行全肺灌洗,了解全肺灌洗對(duì)貧鈾吸入性肺損傷的干預(yù)作用。本課題分為兩部分進(jìn)行,(一)貧鈾吸入性亞急性肺損傷模型的建立;(二)全肺灌洗對(duì)吸入性肺損傷的干預(yù)作用。 第一部分:貧鈾吸入性肺損傷犬模型的建立 目的:建立研究用的貧鈾吸入性亞急性肺損傷犬模型。 方法:將26犬隨機(jī)分為空白對(duì)照組(n=6)、低劑量組(n=10)、高劑量組(n=10),采用經(jīng)氣管插管將不同濃度的貧鈾混懸液分別灌入低劑量組(2mg/kg)和高劑量組(20mg/kg)實(shí)驗(yàn)動(dòng)物左側(cè)肺內(nèi),空白對(duì)照組僅灌入生理鹽水(0.2ml/kg),記錄貧鈾灌注各組動(dòng)物的生存時(shí)間,觀察時(shí)間截止為貧鈾灌注后30天。在灌注后第30天,對(duì)存活犬行肺部CT檢查,處死后取肺組織行病理檢查。 結(jié)果:在30天的觀察期內(nèi),空白對(duì)照組動(dòng)物無(wú)死亡,低劑量組中1只犬在貧鈾灌注后22天死亡,其余犬存活均超過(guò)30天,高劑量組所有犬均在30天內(nèi)死亡,存活時(shí)間11.2±8.9天。高劑量組與低劑量組和對(duì)照組比較,在生存時(shí)間上的差異有統(tǒng)計(jì)學(xué)意義(P0.05),低劑量組與對(duì)照組相比,生存時(shí)間上的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。低劑量組肺組織的病理學(xué)改變主要為肺泡腔內(nèi)炎細(xì)胞滲出、出血及透明膜形成,肺泡壁毛細(xì)血管擴(kuò)張、充血,肺間質(zhì)炎細(xì)胞浸潤(rùn),肺CT主要改變?yōu)樽蠓纹瑺顫B出影及實(shí)變影,腹側(cè)病變重于背側(cè)。 結(jié)論:采用貧鈾混懸液以2mg/kg劑量行單側(cè)肺灌注所建立的動(dòng)物模型,適用于進(jìn)行30天內(nèi)亞急性貧鈾毒性的實(shí)驗(yàn)研究。 第二部分:全肺灌洗對(duì)貧鈾吸入性肺損傷的干預(yù)作用 目的:了解全肺灌洗及不同時(shí)間點(diǎn)灌洗對(duì)貧鈾吸入性肺損傷的治療作用。 方法:以第一部分中的低劑量組(2mg/kg)貧鈾使用劑量建立肺損傷模型并作為研究對(duì)象,將亞急性肺損傷犬隨機(jī)分為對(duì)照組(n=15),早期灌洗組(n=15),晚期灌洗組(n=15),對(duì)早期灌洗組在染毒后第3天、晚期灌洗組在染毒后第14天進(jìn)行左肺大容量全肺灌洗,灌洗后立即回收,檢測(cè)早期灌洗組(3天)、晚期灌洗組(14天)動(dòng)物的支氣管肺泡灌洗液(BALF1)中貧鈾含量。貧鈾灌注30天后,觀察各組動(dòng)物肺部CT影像學(xué)改變,同時(shí)再次進(jìn)行支氣管肺泡灌洗,檢測(cè)不同灌洗組動(dòng)物支氣管肺泡灌洗液(BALF2)中細(xì)胞因子TNF-α及IL-6含量。貧鈾灌注60天后,記錄3組動(dòng)物的生存情況后,處死動(dòng)物,采用鈾熒光發(fā)光法測(cè)定肺組織鈾含量以及細(xì)胞因子TNF-α及IL-6含量。 結(jié)果:早期灌洗組的生存時(shí)間明顯高于對(duì)照組,晚期灌洗組與對(duì)照組比較,生存時(shí)間無(wú)顯著改善。對(duì)貧鈾吸入性肺損傷犬模型進(jìn)行全肺灌洗,早期灌洗組肺泡灌洗液(BALF1)中貧鈾濃度明顯高于晚期灌洗組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。30天后,胸部CT分析顯示,早期灌洗組與對(duì)照組CT評(píng)分具有統(tǒng)計(jì)學(xué)差異(P0.05),晚期灌洗組與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義。對(duì)肺泡灌洗液(BALF2)中細(xì)胞因子TNF-α、IL-6含量檢測(cè)發(fā)現(xiàn),早期灌洗組中TNF-α、IL-6明顯低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),晚期灌洗組與對(duì)照組之間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。60天后處死動(dòng)物檢測(cè)發(fā)現(xiàn),早期灌洗組肺組織的貧鈾含量、肺組織勻漿上清中TNF-α、IL-6均低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),晚期灌洗組肺組織的鈾含量、TNF-α、IL-6與對(duì)照組之間比較無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。 結(jié)論:早期和晚期行全肺灌洗均能洗出一定數(shù)量的貧鈾顆粒,但早期灌洗能顯著延長(zhǎng)貧鈾吸入性肺損傷動(dòng)物的生存期、改善肺部影像學(xué)變化及減輕肺部炎癥反應(yīng)。
[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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R-332;R563
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