20%脂肪乳剂联合氯解磷定及阿托品对有机磷中毒小鼠的脑保护作用研究

doi:10.16138/j.1673-6087.2025.04.07

摘要/Abstract

摘要：

目的：探讨氯解磷定、阿托品联合脂肪乳剂对有机磷中毒小鼠模型的治疗效果。方法：选取80只C57/BL品系实验小鼠，采取随机数字化法分为4组，每组10只。建立有机磷农药小鼠中毒模型，使用氯解磷定、阿托品及脂肪乳剂分组治疗。结果：与仅染毒组相比，治疗组小鼠的肌束震颤强度、翻正反射消失时间显著改善（均P<0.001），且氯解磷定、阿托品和脂肪乳剂联合治疗组改善更明显。联合疗法还可有效调节中毒小鼠血清中乙酰胆碱酯酶（acetylcholinesterase，AchE）、丙二醛（malondialdehyde，MDA）和S100钙结合蛋白B（S100 calcium binding protein B，S100B）水平（均P<0.001），于7 d后恢复至正常范围。在Y迷宫测试中，治疗组小鼠的正确反应次数显著高于染毒组，尤其是脂肪乳剂联合治疗组（均P<0.001）。组织病理学检查显示，氯解磷定与阿托品联用可显著减轻中毒所致脑损伤，加用脂肪乳剂后效果更显著。结论：氯解磷定联合阿托品可有效缓解有机磷中毒小鼠症状，加用脂肪乳剂可进一步增强疗效，为临床治疗提供新策略。

关键词: 有机磷中毒, 阿托品, 氯解磷定, 脂肪乳剂

Abstract:

Objective To investigate the therapeutic effect of pralidoxime combined with atropine and lipid emulsion on a mouse model of organophosphate poisoning. Methods Eighty C57/BL6 strain experimental mice were randomly divided into four groups of 10 each using a digital randomization method. A mouse organophosphate poisoning model was established using organophosphate pesticides. Pralidoxime combined with atropine and lipid emulsion was used for treatment. Results The results showed that compared with the poisoning group, the mice in the treatment group showed significant improvement in physiological indexes such as fasciculation tremor intensity and anti-reflex disappearance time (all P<0.001). In particular, the effect was more pronounced in the combination treatment group with pralidoxime, atropine, and lipid emulsion. In addition, the combination therapy effectively improve the serum levels of acetylcholinesterase (AchE), malondialdehyde (MDA) and S100 calcium binding protein B (S100B) in the poisoning mice (all P<0.001) and promoted the recovery of these biochemical indicators to normal levels after 7 days. In the behavioral test, the number of correct responses in the Y-maze test was significantly higher in the treatment group than in the poisoning group, especially in the mice receiving the combination treatment (all P<0.001). Histopathological examinations showed that the combination of clofosidine and atropine could significantly reduce the brain tissue damage caused by poisoning, and the effect was more significant after the addition of lipid emulsion. Conclusions Pralidoxime combined with atropine can effectively alleviate the symptoms of organophosphate poisoning in mice, and the addition of lipid emulsion can further optimize the therapeutic effect, providing a new treatment strategy for clinical practice.

Key words: Organophosphate poisoning, Atropine, Pralidoxime, Fat emulsion

中图分类号:

R595.4

高慧, 杨超, 胡晓峰. 20%脂肪乳剂联合氯解磷定及阿托品对有机磷中毒小鼠的脑保护作用研究[J]. 内科理论与实践, 2025, 20(04): 301-305.

GAO Hui, YANG Chao, HU Xiaofeng. Study on brain protective effect of 20% lipid emulsion combined with pralidoxime and atropine on organophosphate poisoning mice[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(04): 301-305.

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指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
肌束震颤强度（分）	0	3（3,3）^1）	2（2,2）^1）2）	2（1,2）^1）2）3）	34.536	<0.001
翻正反射消失时间（s）	0	345.700±36.576^1）	541.100±84.608^1）2）	650.300±122.405^1）2）3）	138.900	<0.001

指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
AChE(U/mL)	102.347±16.055	50.880±5.127^1）	73.491±6.843^1）2）	88.732±12.666^1）2）3）	118.9	<0.001
MDA(nmol/mL)	4.423±0.606	6.304±0.645^1）	5.339±0.545^1）2）	4.785±0.404^1）2）3）	64.770	<0.001
S100B(pg/mL)	62.700±14.305	155.731±11.5^1）2）	126.900±17.413^1）2）	111.221±11.511^1）2）3）	235.300	<0.001

指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
AChE(U/mL)	100.843±16.080	47.871±8.759^1）	74.719±12.494^1）2）	82.988±13.343^1）2）3）	87.090	<0.001
MDA(nmol/mL)	4.472±0.469	7.036±1.048^1）	6.118±0.353^1）2）	5.364±0.736^1）2）3）	71.020	<0.001
S100B(pg/mL)	64.994±15.851	601.044±25.228^1）	476.553±25.960^1）2）	421.712±30.092^1）2）3）	2572.000	<0.001