二甲基甲酰胺急性肝损伤与肝脏谷胱甘肽的关系

The relationship between acute liver injury caused by dimethylformamide and glutathione in liver

目的 研究二甲基甲酰胺 (DMF)所致急性肝损伤规律及其与肝脏谷胱甘肽 (GSH)的关系。方法 以 6 0 0、12 0 0、180 0mg/kgDMF分别给小鼠腹腔染毒 ,分析血清山梨醇脱氢酶 (SDH)、丙氨酸转氨酶 (ALT)及肝脏GSH的变化 ,观察病理改变 ;高剂量DMF染毒后 ,再经口连续投入N 乙酰半胱氨酸 (NAC) ,与未投药组比较。结果 低、中、高 3个剂量组的小鼠血清SDH、ALT分别在染毒后 2 4、36、4 8h达高峰 ,2项指标高峰值与DMF剂量呈正相关 (r =0 .95 1,r =0 .997) ,各染毒组肝脏GSH的损耗均早于血清酶的升高 ,分别在染毒后 8、12、2 4h降至最低 ,最低值与DMF剂量呈负相关 (r =- 0 .85 4 )。经口投入NAC后 ,血清SDH、ALT活力的升高及肝脏GSH的损耗及病理改变均明显减轻 ,差异有显著性 (前 2项指标P <0 .0 1,后 1项指标P <0 .0 5 )。结论 DMF急性肝损伤有剂量 -效应和时间 -效应关系 ,随着染毒剂量增加、肝损伤加重、损伤高峰出现时间延迟 ,毒作用机制与肝脏GSH含量降低有关。

Objective To study the acute liver injury caused by N,N dimethylformamide(DMF) and the relationship between this injury and glutathione(GSH) in liver. Methods DMF was administered intraperitoneally to mice by single injection at 600,1 200,1 800 mg/kg respeclively.Mice were sacrificed on scheduled time.After administration of highest dose of DMF,N acetylcysteine(NAC) was successively given to mice per os .Liver injury was measured by changes in plasma levels of sorbital dehydrogenase(SDH),alanine transaminase(ALT) and pathobiology. Results After administration of 600,1 200 or 1 800 mg/kg DMF,the highest levels of SDH and ALT occurred at 24,36,48 hours respectively,correlated with DMF( r =0.951, r =0.997).The depletion of GSH occurred earlier than liver injury and its lowest value appearing at 8,12,24 hour respectively also correlated with DMF( r =-0.854).Successive treatment of mice with NAC protected against both increase of SDH,ALT and decrease of GSH( P <0.05). Conclusion There were dose effect relationship and time effect relationship between DMF and acute liver injury.The maximal toxicity was more serious and occurred later after administration of a higher dose than a lower dose;the hepatotoxicity of DMF might be associated with the lowered content of GSH.