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近年来,核潜艇部队任务繁重,战备训练强度加大,发生核事故的潜在危险随之增加。核潜艇事故发生时可能伴随着核泄漏,艇员暴露于核辐射环境中[1-2]。快速上浮脱险因具有脱险深度大、操作简单、速度快等优点而被作为有效的潜艇脱险方式广泛应用,但快速上浮脱险过程中也存在减压病发生的风险[3]。减压病是由于外界环境压力迅速下降,导致机体组织内溶解的惰性气体溢出形成气泡,从而造成一系列病理反应的疾病[4-5]。快速上浮脱险导致的减压病主要累及心肺系统[6-7],而肺作为对电离辐射敏感的组织之一,在辐射暴露后数小时内即可产生早期辐射损伤[8]。艇员在受到一定剂量核辐射后,是否会增加随后快速上浮脱险所致减压病发生的风险,对于后续救治方案和流程的制定至关重要。
本研究以大鼠为研究对象,建立不同辐射剂量合并特定减压负荷的复合损伤动物模型,观察实验后大鼠的死亡情况,并检测其肺湿干重比、肺组织损伤程度以及肺泡灌洗液中炎症因子和氧化应激相关分子的变化,探讨辐射对快速上浮脱险致减压病发生风险以及肺组织损伤的影响,为失事核潜艇脱险艇员的一线救治提供一定的理论支持。
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由表1可知,单纯减压组和6 Gy照射+减压组各有1只大鼠死亡,4 Gy照射+减压组和8 Gy照射+减压组各有4只大鼠死亡。各组间大鼠死亡率的差异无统计学意义(χ2=7.925, P>0.05),但4 Gy照射+减压组和8 Gy照射+减压组大鼠的死亡率较单纯减压组存在上升趋势。
组别 数量(只) 死亡数量(只) 死亡率(%) 空白对照组 10 0 0 单纯减压组 10 1 10.0 4 Gy照射+减压组 11 4 36.4 6 Gy照射+减压组 11 1 10.0 8 Gy照射+减压组 11 4 36.4 表 1 不同辐射剂量暴露后大鼠减压病死亡情况
Table 1. Death of decompression sickness after exposure to different doses of radiation
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由图1可见,与空白对照组相比,各组大鼠肺湿干重比均有上升趋势,其中6 Gy照射+减压组和8 Gy照射+减压组的差异有统计学意义(F=3.096,LSD-t=2.758、2.959;均P<0.05);与单纯减压组相比,各照射组大鼠肺湿干重比均有上升趋势,但差异无统计学意义(LSD-t=0.901、1.818、2.020,均P>0.05)。
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由图2可见,空白对照组大鼠肺泡及支气管结构基本正常,无炎性细胞浸润;单纯减压组大鼠可见轻度炎性细胞浸润和少量红细胞渗出;4 Gy照射+减压组大鼠肺间质有炎性细胞浸润,可见红细胞渗出,肺泡壁轻度增厚;6 Gy照射+减压组大鼠肺间质增生伴炎性细胞浸润,支气管内少量渗出物,肺泡壁增厚;8 Gy照射+减压组大鼠血管及支气管周围组织增生,内可见炎性细胞浸润及出血灶,部分血管周围明显可见渗出物,肺泡壁增厚,肺泡腔内明显可见渗出物。组织病理学检查结果提示,不同剂量辐射暴露后再进行减压会加重大鼠肺组织水肿及炎性损伤,其中6 Gy照射+减压组和8 Gy照射+减压组大鼠的损伤较为显著。
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由图3可见,与空白对照组比较,各组大鼠肺泡灌洗液中IL-1β、IL-6、TNF-α水平均显著上升(均P<0.01);与单纯减压组比较,各照射组IL-1β、IL-6、TNF-α水平均显著上升(均P<0.01);与4 Gy照射+减压组比较,6 Gy照射+减压组IL-1β、IL-6、TNF-α水平均显著上升(均P<0.01);而与6 Gy照射+减压组比较,8 Gy照射+减压组IL-1β、IL-6、TNF-α水平则显著下降(均P<0.05);4 Gy照射+减压组与8 Gy照射+减压组比较,差异均无统计学意义(LSD-t=0.624、0.587、0.922,均P>0.05)。
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由图4可见,与空白对照组比较,各组大鼠肺泡灌洗液中SOD活力、GSH-Px水平均显著下降(F=35.720、51.370,LSD-t=6.267~13.107;均P<0.01);与单纯减压组比较,各照射组大鼠SOD活力、GSH-Px水平显著下降(LSD-t=2.716~5.154,均P<0.01);各照射组间的差异无统计学意义,但6 Gy照射+减压组大鼠SOD活力、GSH-Px水平下降幅度最大。
图 4 不同剂量辐射暴露后各组大鼠肺泡灌洗液SOD活力、GSH-Px及MDA水平的变化
Figure 4. Changes of superoxide dismutase, glutathione peroxidase, malondialdehyde levels in bronchoalveolar lavage fluid in each group of rats after different doses of radiation exposure
与空白对照组比较,各组大鼠肺泡灌洗液MDA水平均显著上升(F=45.680,LSD-t=4.395~12.752;均P<0.01);与单纯减压组比较,各照射组大鼠MDA水平显著上升(LSD-t=3.198~8.017,均P<0.01);与4 Gy照射+减压组比较,6 Gy照射+减压组大鼠MDA水平显著上升(P<0.01),8 Gy照射+减压组的差异无统计学意义(LSD-t=0.541,P>0.05);而与6 Gy照射+减压组比较,8 Gy照射+减压组则显著下降(LSD-t=4.204,P<0.01)。
辐射合并减压暴露致大鼠急性肺损伤的效应观察
Effects of radiation combined with decompression exposure on acute lung injury in rats
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摘要:
目的 探讨不同剂量辐射暴露对快速上浮脱险致大鼠减压病急性肺损伤及死亡率的影响。 方法 53只SD大鼠按体重分层后以随机数表法分为5组:空白对照组(10只)、单纯减压组(10只)、4 Gy照射+减压组(11只)、6 Gy照射+减压组(11只)以及8 Gy照射+减压组(11只)。照射组大鼠先进行4、6、8 Gy不同剂量60Co γ射线全身照射,空白对照组及单纯减压组大鼠在相同环境下不进行照射;照射结束后1 h各减压组再进行减压处理实验(57 m停留45 min后,37 s快速减压至大气压),观察各组大鼠死亡率、肺湿干重比、肺组织病理损伤程度以及肺泡灌洗液中炎症因子和氧化应激相关分子水平的变化。各组大鼠死亡率的比较采用卡方检验,其他指标的比较采用单因素方差分析,进一步两两比较采用LSD-t检验。 结果 与空白对照组比较,各实验组大鼠死亡数量和肺湿干重比均增加,6 Gy照射+减压组和8 Gy照射+减压组大鼠肺湿干重比显著增加,且差异有统计学意义(F=3.096,LSD-t=2.758、2.959;均P<0.05);各实验组大鼠肺组织病理损伤明显,其中6 Gy照射+减压组和8 Gy照射+减压组更为显著;各实验组大鼠肺泡灌洗液中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和丙二醛(MDA)水平显著增加,且差异有统计学意义(F=45.680~78.270,均P<0.01),超氧化物歧化酶(SOD)活力和谷胱甘肽过氧化物酶(GSH-Px)水平显著下降,且差异有统计学意义(F=35.720、51.370,均P<0.01)。与单纯减压组比较,4 Gy照射+减压组和8 Gy照射+减压组大鼠死亡数量增加,但死亡率的差异无统计学意义(χ2=7.925,P>0.05);各照射组大鼠肺湿干重比虽有上升趋势,但差异无统计学意义(LSD-t=0.901、1.818、2.020,均P>0.05);各照射组大鼠肺组织病理损伤有不同程度的加重,其中8 Gy照射+减压组损伤程度最重;各照射组大鼠肺泡灌洗液中炎症因子(IL-1β、IL-6、TNF-α)和氧化应激相关分子(SOD、GSH-Px、MDA)均变化显著(LSD-t=3.081~8.265,均P<0.01),其中6 Gy照射+减压组变化最为显著。 结论 辐射会加重快速上浮脱险造成的肺组织炎症和氧化应激损伤,表现为肺组织病理损伤程度加重及死亡率增加,从而增加快速上浮脱险致减压病发生的风险。 Abstract:Objective To investigate the effects of different doses of radiation exposure on acute lung injury and mortality from decompression sickness (DCS) induced by rapid floating escape in rats. Methods A total of 53 Sprague-Dawley rats were stratified in accordance with body weight and divided into 5 groups by using a random number table method. The groups were as follows: blank control group (10 rats), simple decompression group (10 rats), 4 Gy irradiation with decompression group (11 rats), 6 Gy irradiation with decompression group (11 rats), and 8 Gy irradiation with decompression group (11 rats). The animals in the irradiation groups were given different doses of 60Co γ whole-body radiation and then exposed to decompression treatment (i.e., after staying at a depth of 57 m for 45 min, the rats were made to ascend quickly to atmospheric pressure within 37 s) 1 h after irradiation. The mortality rate, lung wet-dry weight ratio, degree of lung tissue pathological damage, and changes in levels of inflammatory factors and oxidative stress-related molecules in the alveolar lavage fluid were observed in each group of rats. Mortality rates among groups were compared using Chi-square test, while the remaining variables were analyzed using one-way ANOVA. Further comparison between two groups using LSD t-test. Results Compared with that in the blank control group, the number of animal deaths and the lung wet-dry weight ratio increased in each experimental group, with the lung wet-dry weight ratio increasing significantly in the 6 Gy and 8 Gy irradiation with decompression groups (F=3.096, LSD-t=2.758, 2.959; all P<0.05). The pathological damage of lung tissues in each experimental group was evident, and those in the 6 Gy and 8 Gy irradiation with decompression groups were more significant among the irradiation groups. The interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) in the bronchoalveolar lavage fluid of each experimental group were significantly increased (F=45.680–78.270, all P<0.01), whereas superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly decreased (F=35.720, 51.370; both P<0.01). Compared with that in the simple decompression group, the number of animal deaths in the 4 Gy and 8 Gy irradiation with decompression groups increased, but no statistical difference was noted in the mortality rate (χ2=7.925, P>0.05). Although the lung wet-dry weight ratio of the rats in each irradiation group exhibited an upward trend, no statistically significant difference was found (LSD-t=0.901, 1.818, 2.020; all P>0.05). The pathological damage of lung tissues was aggravated to different degrees, and the damage degree of the 8 Gy irradiation with decompression group was the most serious. Inflammatory factors (IL-1β, IL-6, and TNF-α) and oxidative stress-related molecules (SOD, GSH-Px, and MDA) in bronchoalveolar lavage fluid changed significantly (LSD-t=3.081–8.265, all P<0.01). Among which, the 6 Gy irradiation with decompression group exhibited the most significant change. Conclusions Nuclear radiation can worsen lung tissue inflammation and oxidative stress damage caused by rapid floating escape. Such effect is manifested as aggravated lung tissue pathological damage and increased mortality, increasing the risk of DCS caused by rapid floating escape. -
表 1 不同辐射剂量暴露后大鼠减压病死亡情况
Table 1. Death of decompression sickness after exposure to different doses of radiation
组别 数量(只) 死亡数量(只) 死亡率(%) 空白对照组 10 0 0 单纯减压组 10 1 10.0 4 Gy照射+减压组 11 4 36.4 6 Gy照射+减压组 11 1 10.0 8 Gy照射+减压组 11 4 36.4 -
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