巯基化合物对二甲基甲酰胺急性中毒的解毒实验研究

Experimental study on detoxication effect of sulfhydryl compounds in acute poisoning of dimethylformamide

目的 观察二甲基甲酰胺（DMF）急性中毒对小鼠肝组织氧化酶／抗氧化酶系统的影响及不同巯基化合物对肝脏的保护作用。方法 采用DMF灌胃制备小鼠急性中毒模型；于中毒后6、12、24、48和72h取小鼠肝左叶，测定各组肝组织超氧化物歧化酶（SOD）、黄嘌呤氧化酶（XOD）活性的动态变化。采用制备中毒模型后腹腔注射二巯基丙磺酸钠（Na-DMPS）、二巯基丁二酸（DMSA）、还原型谷胱甘肽（GSH）、N-乙酰半胱氨酸（NAC）四种巯基化合物的方法，观察其对DMF急性中毒小鼠的保护作用；并设相应给药的4种药物对照组。DMF灌胃后24h取肝左叶，测定各组肝组织SOD和XOD活性。结果 DMF灌胃后24h小鼠肝组织XOD、SOD活性均明显升高（P均〈0．01），48～72h恢复至正常水平。用Na—DMPS、NAC、DMSA治疗后24h，肝组织SOD、XOD活性较中毒模型组均明显下降（P〈0．05或P〈0．01）；GSH治疗24h后，肝组织XOD活性较中毒模型组明显下降（P〈0．05），SOD则无显著变化（P〉0．05）。4种药物比较，Na—DMPS、NAC和DMSA对SOD的作用比GSH好（P均〈0．05），以Na—DMPS最佳，但Na—DMPS、NAC和DMSA组间比较差异无显著性。4种巯基化合物对XOD的影响差异均无显著性。结论 DMF干扰了体内的氧化酶／抗氧化酶系统，可能是其导致肝损伤的机制之一。Na-DMPS、NAC和DMSA可通过平衡氧化酶／抗氧化酶系统保护肝功能。

Objective To study the change in oxidase and antioxidase in liver of the mice poisoned by dimethylformamide （DMF）, and the effects of the treatment with sulfhydryl compounds in acute poisoning of DMF. Methods The sulfhydryl compounds included sodium dimercaptopropan （Na -DMPS）, N - acetylcysteine （NAC）, glutathione （GSH） and dimercaptosuccinic acid （DMSA）. The model of acute poisoning with DMF in mice was reproduced, and the left hepatic lobes were harvested at 6, 12, 24, 48 and 72 hours after DMF to detect the dynamic changes in the activities of superoxide dismutase （SOD） and xanthine oxidase （XOD） in liver homogenate. Treatment groups included intraperitoneal injection of Na - DMPS, NAC, GSH, DMSA respectively. In the control groups, the activities of XOD and SOD in liver were determined 24 hours after intragastric administration of DMF. Results The activities of XOD, SOD in liver were elevated at 24 hours after intragastric administration of DMF （both P〈0.01）, and returned to the normal levels at 48 - 72 hours. Compared to the poisoning group, the activities of XOD, SOD in liver homogenate were significantly lowered after the treatment of Na- DMPS, NAC and DMSA （P〈0.05 or P〈0. 01 ）. The activity of XOD in liver homogenate was reduced 24 hours after treating with GSH （P〈 0.05）, and no obvious change was observed in SOD （P〉0.05）. As far as the activity of SOD was concernd, Na-DMPS, NAC, DMSA showed better effects than GSH （all P〈0.05）, and Na- DMPS was the best. There was no significant differences in XOD among the four sulfhydryl compounds. Conclusion The balance of oxidase and antioxidase is interrupted by DMF, which might be one of the mechanisms of damage to the liver. Na -DMPS, NAC and DMSA could protect liver function by restoring the balance.