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中华卫生应急电子杂志

中华卫生应急电子杂志 ›› 2017, Vol. 03 ›› Issue (02) : 79 -87. doi: 10.3877/cma.j.issn.2095-9133.2017.02.004

所属专题： 专题评论； 文献；

论著

军用密闭舱室有毒烟雾致急性肺损伤的组合救治方案的评价
孙磊1, 陈晟1, 蔡颖1, 安辉1, 刘晋祎1, 杨桓1, 敖琳2, 陶成玉3, 曹佳1,†()   
  1. 1. 400038　重庆，第三军医大学毒理学研究所
    3. 233010　蚌埠，解放军装甲兵学院门诊部
  • 收稿日期:2016-11-25 出版日期:2017-04-18
  • 通信作者: 曹佳
  • 基金资助:
    全军部队卫生和疾病防控应用性研究指令性课题(13BJYZ28)

Effect of combined treatments on acute lung injury induced by smoke inhalation in military airtight cabins in rats

Lei Sun1, Sheng Chen1, Ying Cai1, Hui An1, Lin Ao1, Huan Yang1, Chengyu Tao2, Jinyi Liu3, Jia Cao1,†()   

  1. 1. Institute of Toxicology, Third Military Medical University, Chongqing 400038, China
    2. Department of Ambulant Clinic, PLA Academy of Armored Forces, Bengbu 233010, China
  • Received:2016-11-25 Published:2017-04-18
  • Corresponding author: Jia Cao
  • About author:
    Corresponding author: Cao Jia, Email:
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引用本文：

孙磊, 陈晟, 蔡颖, 安辉, 刘晋祎, 杨桓, 敖琳, 陶成玉, 曹佳. 军用密闭舱室有毒烟雾致急性肺损伤的组合救治方案的评价[J]. 中华卫生应急电子杂志, 2017, 03(02): 79-87.

Lei Sun, Sheng Chen, Ying Cai, Hui An, Lin Ao, Huan Yang, Chengyu Tao, Jinyi Liu, Jia Cao. Effect of combined treatments on acute lung injury induced by smoke inhalation in military airtight cabins in rats[J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2017, 03(02): 79-87.

目的

评价4种有效单项治疗措施的不同组合治疗方案对密闭舱室烟雾吸入性急性肺损伤(ALI)的救治效果，并筛选出最佳组合方案。

方法

将78只清洁级雄性SD大鼠[7～9周龄，体重(220±16)g]按随机数字表法分为3个组，分别为正常对照组(A组，6只)、烟雾吸入损伤组(B组，6只)和治疗组(66只)进行随机对照研究。治疗组再随机分为11个亚组(C～M组，每组6只)，其中C～F组分别进行100%浓度常压氧吸入、50 U/mL肝素钠雾化吸入、5 mg/kg地塞米松(Dex)预处理、200 mg/kg N-乙酰半胱氨酸(NAC)预处理4种单项治疗措施；G～M组大鼠分别进行上述2种(G组：肝素钠雾化吸入＋100%常压氧；H组：Dex预处理＋100%常压氧；I组：NAC预处理＋100%常压氧)、3种(J组：Dex预处理＋肝素钠雾化吸入＋100%常压氧；K组：NAC预处理＋肝素钠雾化吸入＋100%常压氧；L组：NAC预处理＋Dex预处理＋100%常压氧)和4种措施(M组)的联合处理，各联合治疗组的治疗方法同各单项治疗组。观察烟雾吸入后24 h各组大鼠的动脉血气分析[动脉学氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)和酸碱度(pH)]、静脉血碳氧血红蛋白(COHb)水平及其清除率(CCR)、肺组织病理改变及评分、肺湿干重比值(W/D)、肺通透性指数(PPI)、肺组织谷胱甘肽-过氧化物酶(GSH-Px)活性、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量以及血清一氧化氮(NO)含量等指标，综合评价各种组合措施的综合救治效果。

结果

烟雾吸入后24h，各联合治疗组中G、H和J组大鼠动脉血PaO2显著高于B组[(106.0±9.2)mmHg，(108.1±10.9)mmHg，(108.1±4.3)mmHg vs (89.1±11.5)mmHg，P<0.01或0.05]；G ～ M联合治疗组大鼠在烟雾吸入染毒后1 h的CCR均高于B组(P<0.01或0.05)；G～M联合治疗组大鼠肺组织病理损伤总分均低于B组[(6.1±1.8)分，(4.4±1.1)分，(5.1±1.0)分，(3.6±1.2)分，(4.2±0.7)分，(6.0±1.0)分，(4.2±0.6)分vs(9.4±1.2)分，P均<0.01]；与B组比较，E和M组PPI显著下降(2.42±0.38，1.96±0.91 vs 7.02±1.05，P均<0.01)，H、J、L、M组W/D显著降低(4.63±0.08，4.58±0.06，4.47±0.14，4.49±0.13 vs 4.88±0.21，P<0.01或0.05)；G、I、K、L和M组大鼠肺组织内GSH-Px活性均高于B组[(108.1±3.5)U/mgprot，(125.0±6.3)U/mgprot，(151.2±29.6)U/mgprot，(125.1±25.6)U/mgprot，(139.4±30.0)U/mgprot vs(95.8±12.1)U/mgprot，P<0.01或0.05)]，G、J、K、L和M组大鼠肺组织SOD活性高于B组，且G、H、I、J和L组大鼠肺组织MDA含量低于B组(P<0.01或0.05)；所有联合治疗组大鼠的血清NO含量均低于B组(P<0.01或0.05)；各组方中M综合救治措施缓解的指标数最多为8项，且其半定量评分分值最高(15分)。

结论

NAC、Dex预处理、肝素钠雾化吸入、常压纯氧吸入4种措施的各种组合间对烟雾吸入性ALI存在着独特的互补或拮抗效应；其中NAC、Dex预处理、肝素钠雾化吸入和常压纯氧吸入4种措施的联合治疗方案对ALI具有最全面的救治效果，可认为在多种救治措施组合中是一种最理想的综合治疗方式。

关键词: 军用密闭舱室, 火灾, 烟雾吸入, 吸入性肺损伤, 救治措施
Objective

To screen and evaluate the therapeutic effect of various combined treatments on acute lung injury (ALI) of rats induced by smoke inhalation in military airtight cabins.

Methods

A total of 78 male SD rats were randomly divided into control group (Group A), injury group (Group B), single treatment groups (Groups C-F) and combined treatment groups (Groups G-M), with 6 rats per group. Groups C-F were treated with oxygen inhalation, heparin sodium nebulization, dexamethasone (Dex) or N-acetylcysteine (NAC) pre-injection, respectively, while Groups G-M were treated with a combination of two or more therapeutic measures above. Blood gas [arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and pH], carbon oxygen hemoglobin (COHb) and its clearance rate (CCR), lung pathological changes, lung wet-to-dry weight ratio (W/D), pulmonary permeability index (PPI), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity and the content of malonaldehyde (MDA) and nitric oxide (NO) were measured at 24 h post-exposure to evaluate the effects of the various therapeutic measures.

Results

Compared with Group B, the PaO2 was increased significantly in Groups G, H and J [(89.1±11.5) mmHg vs (106.0±9.2) mmHg, (108.1±10.9) mmHg and (108.1±4.3) mmHg, P<0.01 or 0.05]. CCR in Groups G-M was significantly higher than that in Group B (P<0.01 or 0.05). Lung pathological score in Groups G~M as decreased significantly compared with Group B (P<0.01). PPI in Group E and M was decreased significantly compared with Group B (2.42±0.38, 1.96±0.91 vs 7.02±1.05, P<0.01). W/D in Groups H, J, L and M was decreased significantly compared with Group B (4.63±0.08, 4.58±0.06, 4.47±0.14, 4.49±0.13 vs 4.88±0.21, P<0.01 or 0.05). GSH-Px activity was significantly increased in Groups G, I, K, L and M compared with Group B [(108.1±3.5)U/mgprot, (125.0±6.3) U/mgprot, (151.2±29.6)U/mgprot, (125.1±25.6)U/mgprot, (139.4±30.0)U/mgprot vs (95.8±12.1)U/mgprot, P<0.01 or 0.05)]. SOD activity significantly was increased in Groups G, J, K, L and M and the content of MDA significantly decreased in Groups G, H, I, J and L compared with Group B (P<0.01 or 0.05). The content of NO was decreased significantly in Groups G~M compared with Group B (P<0.01 or 0.05). The indices related with ALI which could be ameliorated with treatments were the most in Group M among Groups G-M and the semi quantitative score was highest in Group M.

Conclusion

The combined treatment of NAC and Dex pre-injection, high concentration of heparin sodium nebulization and oxygen inhalation is the most effective and comprehensive therapy for ALI induced by smoke inhalation in rats among different combinations.

Key words: Military airtight cabin, Fire, Smoke inhalation, Inhalation lung injury, Therapeutic measure
图1 不同组合救治方案治疗组大鼠烟雾吸入后24 h动脉血气分析结果
图2 不同组合救治方案治疗组大鼠烟雾吸入后20min、80min时血COHb%及CCR的比较
图3 不同组合救治方案治疗组大鼠烟雾吸入后24 h肺组织损伤评分的比较
图4 不同组合救治方案治疗组大鼠烟雾吸入后24 h肺含水量比较
表1 不同救治措施组大鼠烟雾吸入后24 hBALF及血清中总蛋白浓度比较
组别 BALF(μg/uL) 血清(μg/uL) PPI
A组 0.05±0.01 49.1±4.1 1.00±0.27
B组 0.25±0.06c 35.9±9.8 7.02±1.05c
C组 0.23±0.10 49.9±2.4 4.77±2.15
D组 0.24±0.05 48.5±6.4 5.15±1.62
E组 0.12±0.01 51.0±11.6 2.42±0.38b
F组 0.25±0.07 51.5±2.8 4.91±1.55
G组 0.43±0.22 34.0±6.5 12.76±5.71
H组 0.21±0.07 37.1±3.9 5.72±2.05
I组 0.31±0.13 35.1±4.0 8.76±3.61
J组 0.19±0.03 41.4±3.0 4.60±0.84
K组 0.16±0.04 35.2±2.4 4.58±1.08
L组 0.21±0.04 43.8±5.2 4.87±1.20
M组 0.08±0.04a 41.2±5.0 1.96±0.91b
图5 不同组合救治方案治疗组大鼠烟雾吸入后24 h肺组织GSH-PX、SOD活性和MDA含量比较
图6 不同组合救治方案治疗组大鼠烟雾吸入后24 h肺组织MDA含量比较
图7 不同组合救治方案治疗组大鼠烟雾吸入后24 h血清NO含量比较
表2 各联合治疗方案疗效的综合评分表
组别 主要检测指标 缓解指标数(项) 半定量评分
PaCO2 PaO2 CCR Histology W/D PPI GSH-Px SOD MDA NO
C 1 2 2 0 0 0 －1 2 0 1 5 7
D 1 2 0 2 1 0 0 2 0 0 5 8
E 0 1 0 2 1 2 0 0 0 1 5 7
F 0 0 0 2 0 0 2 2 2 1 5 9
G 0 1 2 2 0 0 1 1 1 2 7 10
H 0 1 2 2 1 0 0 0 2 2 6 10
I 0 0 1 2 0 0 2 －1 2 1 5 7
J 0 2 1 2 2 0 0 2 1 1 7 11
K 0 0 2 2 0 0 2 2 0 2 5 10
L 0 0 2 2 2 0 1 1 2 2 7 12
M 1 0 2 2 2 2 2 2 0 2 8 15
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