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二甲基甲酰胺对动物的急性毒性实验研究 被引量:13

Experimental study on acute dimethylformamide poisoning and detoxifcation in mice and rabbits
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摘要 目的观察动物二甲基甲酰胺(DMF)急性中毒表现、病理变化及几种药物对其急性中毒保护作用。方法建立DMF急性经口中毒小鼠和兔实验模型,观察中毒小鼠和兔组织病理学及酶学变化、不同剂量DMF中毒表现,测定小鼠经口LD50,观察不同保护药物〔N-乙酰半胱氨酸(NAC)、谷胱甘肽(GSH)、二巯丙磺钠(Na-DMPS)、二巯丁二酸(DMSA)、东莨菪碱(SCO)〕对小鼠生存时间及存活率的影响。结果DMF染毒剂量越大,中毒潜伏期越短,生存时间越短,小鼠经口LD50为6.019gkg。中毒主要表现有行动迟缓、行走不稳、发绀、易兴奋、呼吸急促、四肢抽搐等;血AST、ALT及LDH升高。病理学检查见:胃肠散在小充血灶;腹腔内少许淡黄色或淡血性腹水;肝细胞局灶坏死、炎症细胞浸润,肝血窦扩张、淤血,部分肝细胞索断裂,线粒体水肿、嵴减少,肝细胞内胆汁淤积;肾小管上皮细胞水肿,局部肾小管细胞核固缩、碎裂,胞质内板层小体形成,近曲小管微绒毛细丝样改变,线粒体可见电子致密物。GSH、SCO、Na-DMPS可延长小鼠急性DMF中毒的生存时间。NAC、GSH、Na-DMPS、DMSA、SCO对致死亡剂量的DMF中毒小鼠生存时间及存活率无显著影响。结论DMF是一种低毒毒物,急性经口中毒表现多样,主要损害脏器为肝、肾,GSH、SCO、Na-DMPS对DMF中毒可能有保护作用。 Objective To observe the intoxicated symptoms,pathology changes of acute poisoning of dimethylformamide (DMF) and the detoxification with several protective drugs. Methods The model of acute poisoning of DMF by oral administration in mice and rabbits was established, the histopathological changes and plasma enzymes were observed, the intoxicated manifestation were recorded at different dosages. LD50 was tested. The "effects of five protective drugs(N-acetylcysteine NAC, glutathione GSH, sodium dimercaptopropan Na-DMPS, dimercaptosuccinic acid DMSA,scopolamine SCO) were observed in mice poisoned by DMF. Results The higher dosage of DMF was used, there were the shorter latent period and survival duration in mice and rabbits. The LD50 of DMF in mice was 6.019 g/kg. The intoxicated symptoms, such as torpidity, ataxia, cyanosis, convulsion and dyspnea were observed. Plasma AST, ALT and LDH increased. Histopathological examination showed spot hyperaemia in stomach, intestine and ascites was displayed; local liver necrosis, infiltration of inflammatory cells, dilation and congestion in hepatic sinusoid, breakage in partial liver cell cords were also shown; Mitochondria swelling, decrease of mitochondrial crista , and cholestasis in the hepatic cells were found. Swelling of the epithelial cells, karyopyknosis, nuclear fragmentation, and internal lamellar body in cytoplasm were seen in the renal tubules. Filament-like alteration in microvilli and electron-dense deposits in mitochondria (calcareous infarct) of epithelial cells in the proximal convoluted tubules were also found. The survival duration of mice poisoned by DMF could be prolonged by GSH, SCO and Na-DMPS. The survival duration and survival rates in mice at the lethiferous dosage of DMF were not significantly changed by NAC, GSH, Na-DMPS, DMSA and SCO. Conclusion DMF is a hypo-venenosus poison. The intoxicated symptoms are various by oral administration. The primary damaged visceras by DMF are liver and kidney. GSH, SCO, NaDMPS may have the protective effects for poisoning by DMF.
出处 《浙江医学》 CAS 2006年第5期349-352,F0002,共5页 Zhejiang Medical Journal
基金 温州市科技局资助项目(Y2004A130)
关键词 二甲基甲酰胺 急性中毒 Dimethylformamide Acute poisoning
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