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目的探讨N,N-二甲基甲酰胺(DMF)对C57BL/6雄性小鼠肝脏的急性毒性效应。方法 32只雄性C57BL/6小鼠随机分为4组,每组8只。2、3、4组单次经口染毒1 500 mg/kg(bw DMF后分别在24 h,48 h,72 h处死。1组为空白对照组。记录各组小鼠染毒前后的体重并计算肝脏系数。摘眼球取血并分析血生化指标,光镜下观察肝组织切片检查肝脏损伤情况;LC-MS/MS检测小鼠血液中N-甲基氨基甲酰加合物(NMHb)含量。结果与对照组相比,染毒后各组肝脏系数差异均有统计学意义(F=5.837,P<0.05)。24 h时血清丙氨酸氨基转移酶(ALT)水平升高且差异有统计学意义(F=17.173,P<0.05);肝脏出现多灶性水样变伴小的坏死灶,表现出较明显的肝脏毒性效应。48 h时毒性效应进一步加重,ALT、AST(天门冬氨酸转移酶)升至高峰(F=17.173,P<0.05;F=17.633,P<0.05),镜下呈弥漫性肝细胞坏死及炎细胞浸润等病理改变。染毒后72 h时毒性效应减轻,ALT、AST较48 h时有所下降,但与对照组比较差异仍有统计学意义(F=17.173,P<0.05;F=17.633,P<0.05);肝脏以弥漫性水样变和点状坏死为主,病变程度有所减轻。2、3、4组小鼠血液NMHb含量分别为18.56±9.60、22.35±7.66和19.55±3.56 nmol/g globin,1组无检出。结论 DMF可以引起C57BL/6雄性小鼠急性肝毒性损伤并在48h左右达到高峰;NMHb可以在DMF染毒小鼠血液样本中检出。
Objective To investigate the acute toxicity of N, N-dimethylformamide (DMF) to the liver of C57BL / 6 male mice. Methods Thirty-two male C57BL / 6 mice were randomly divided into 4 groups with 8 mice in each group. The mice in groups 2, 3, and 4 were orally exposed to 1 500 mg / kg (bw DMF for 24 h, 48 h and 72 h respectively), and the control group was taken as blank control group The liver index was calculated and the blood was taken from the eye and the blood biochemical parameters were analyzed. The liver damage was observed under light microscope. The content of N-methylcarbamoyl adduct (NMHb) Content.Results Compared with the control group, the liver coefficient of each group after treatment was significantly different (F = 5.837, P <0.05), serum alanine aminotransferase (ALT) level increased at 24 h (F = 17.173, P <0.05). The liver showed multifocal water samples with small necrosis and showed obvious liver toxicity effect. The toxic effects further aggravated at 48 h, ALT, AST (F = 17.173, P <0.05; F = 17.633, P <0.05). Pathological changes such as diffuse necrosis of hepatocytes and infiltration of inflammatory cells were found in the microscope.At 72 h after treatment, the toxicity (P <0.05); F = 17.633, P <0.05); the liver was diffused by water sample change And dotted bad And the degree of lesion was alleviated.2, The blood levels of NMHb in groups 2, 3 and 4 were 18.56 ± 9.60,22.35 ± 7.66 and 19.55 ± 3.56 nmol / g globin, respectively, but no one was detected in group 1. Conclusion DMF can cause C57BL / 6 male mice with acute hepatotoxic injury peaked at around 48 h; NMHb was detected in blood samples from mice exposed to DMF.