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纳洛酮对急性CO中毒大鼠血清MDA、GSH-Px和SOD水平的影响

来源:转载  发布时间:2010/12/11 18:46:22

 

【摘要】目的探讨急性一氧化碳中毒(ACOP)大鼠血清丙二醛(MDA)水平、谷胱甘肽过氧化物酶(GSH-Px)及超氧化物歧化酶(SOD)活性变化及纳洛酮的干预作用,加深对ACOP病理机制及纳洛酮治疗机制的认识。方法 随机将ACOP大鼠分为正常组、对照组和纳洛酮干预组,分别于中毒后0122436小时观察大鼠血清中MDA水平及GSH-PxSOD活性的变化。结果中毒对照组与正常组比较,血清SODGSH-PX活性水平低于正常组(P0.05),血清MDA水平高于正常组(P0.05);纳洛酮干预治疗组中,血清SODGSH-PX活性水平高于对照组(P0.05),血清MDA水平低于对照组(P0.05)。结论 ACOP时血清MDA水平升高,SODGSH-Px活性降低,提示ACOP后存在着严重的自由基氧化损伤过程;纳洛酮干预治疗能提高SODGSH-Px活性水平,降低中毒大鼠血清MDA水平,减轻中毒后自由基氧化损伤的程度。

    
【关键词】急性一氧化碳中毒 丙二醛 超氧化物歧化酶 谷胱甘肽过氧化物酶 脂质过氧化   纳洛酮
    The Effect of Naloxone on Concentration Levels of MDASOD and GSH-Px in Serum of the Rats with Acute Carbon Monoxide Poisoning Li Zili Kang Xuewen Guo Yuxue et al.  Lanzhou Emergency center of Gansu Province Lanzhou 730030

    
Abstract 

    Objective: The purpose of the present study was to evaluate if Naloxone could affect the concentration levels of Malondialdehyde(MDA)
Superoxide dismutase(SOD) and Glutathion peroxidase(GSH-Px) in serum of rats with acute carbon monoxide poisoning(ACOP). 

    Methods: The 100 healthy Wistar rats at first were randomly divided into the control group (10 rats) and therapy group (90 rats). The experimental models of ACOP were established according to the Ishiropoulos method. And then 80 successful ACOP rats model were divided into oxygen therapy group and Naloxone therapy group. For each rat serum samples were obtained and stored respectively at 0h
12h24h and 36h time points for analysis. Finally SOD GSH-Px activity and MDA concentrations in serum were measured. All data were analyzed using SPSS package for Window and significant difference was P value< 0.05. 

    Results: The concentrations of MDA in the tow ACOP groups were significantly higher at each time points than control group (p<0.05)
and significant difference was found between the oxygen group and Naloxone therapy group. The activity of SOD and GSH-Px in the two therapy groups were significantly elevated  when it compared with control group (p<0.05). And the concentrations of SOD and GSH-Px between the oxygen and Naloxone groups were shown significantly different (p<0.05). 

    Conclusion: The demonstrated free radical injury may play an important role in pathogenesis resulting from CO poisoning. Naloxone could reduce the injuries and protected  the cell by significantly affecting  MDA production and SOD
GSH-Px activity after ACOP.    

    
Key words Aarbon monoxide poisoning     Malondialdehyde     Superoxide dismutase     Glutathione peroxidase    Lipoperoxidation    Naloxone
    急性一氧化碳中毒(acute carbon monoxide poisoning ACOP)及其后的氧疗过程中,随着微循环的改善、组织供氧的恢复,组织存在着缺血-再灌注的病理过程,自由基氧化损伤是缺血-再灌注损伤的一个重要方面[1-3]ACOP时纳洛酮能明显缩短昏迷时间,降低ACOP的致残率和死亡率[4],已经逐渐成为ACOP时的常规治疗之一,本研究探讨纳洛酮是否能减轻再灌注损伤,加深对其治疗机制的认识。
    1. 材料与方法

    1.1 
动物分组及模型制备:健康成年雄性Wistar大鼠100只,由兰州大学医学院实验动物中心提供,体重(200±20)g,按照随机数字表法分为正常组(10),中毒组(90),参照Ishiropoulos[5]的方法,自制容器5LCO染毒瓶,中毒组大鼠置于染毒瓶中静式吸入CO 60min,染毒过程中每隔15min测定瓶中CO浓度,根据测定浓度结果补入CO,使瓶内CO浓度维持在(25003500)×10-6 g/m3 。染毒后46min大鼠出现躁动,89min四肢瘫软无力、呼吸急促、呼吸幅度明显增大,25min大鼠全部昏迷,继续染毒至60min后出染毒瓶,置于密闭透明塑料箱中,持续常压吸氧至实验结束,吸入氧浓度为40%,实验期间室内温度在2025,给予大鼠足量的食物和水。90只中毒组大鼠制模染毒成功80只,中毒死亡10只,将中毒大鼠随即分为对照组和干预组,对照组给予持续常压吸氧治疗,吸氧浓度40%,干预组在对照组治疗的基础上给予纳洛酮(北京四环医药)2mg/Kg腹腔注射治疗,每6小时腹腔注射一次。 

    1.2
检测指标及方法:标本采集:分别于染毒结束后即刻、12h24h36h分别处死10只,取血6ml,分离血清进行检测;检测:血清MDA检测采用硫代巴比妥酸比色法;血清SOD活性检测采用黄嘌呤氧化法测定;血清GSH-Px活性检测采用酶促反应谷胱甘肽消耗法测定酶的活性;试剂由南京建成生物工程研究所提供,严格按说明书操作检测。

    1.3
统计学处理:数据资料由SPSS软件处理,采用差表示,利用t检验进行统计分析。以P<0.05表示差异有显著性。
    2  结果

    2.1 ACOP
时,正常组、对照组、干预组大鼠血清MDA水平、SODGSH-Px活性变化见表。
表:ACOP时,正常组、对照组、干预组大鼠血清MDA水平、SODGSH-Px活性变化 
  
例数
0h
12h
24h
36h
MDA
正常组
10
2.58±0.82
2.75±0.92
2.30±0.75
2.10±0.81
对照组
40
3.01±1.25
3.80±1.34
3.60±1.32
3.08±1.04
干预组
40
3.07±1.25
3.09±1.06
2.98±0.91
2.56±0.96
SOD
正常组
10
47.3±15.7
51.3±16.4
52.3±15.9
52.5±16.3
对照组
40
35.3±12.9
32.8±10.3
35.8±13.2
38.2±12.3
干预组
40
35.5±12.4
42.3±13.6
45.4±14.3
48.2±15.4
GSH-Px
正常组
10
36.7±11.2
40.6±12.7
42.2±13.4
43.6±15.6
对照组
40
27.7±8.7
26.2±8.9
25.3±7.7
33.5±10.9
干预组
40
26.9±8.6
35.3±10.8
34.7±12.3
38.7±12.3

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