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目的观察28 d经皮给予较高剂量二氯甲烷后SD大鼠的毒性反应。方法实验设1个溶剂对照组(橄榄油)、4个二氯甲烷染毒组(0.75、1.5、3.0和6.0 g/kg·BW)和1个恢复组(6.0 g/kg·BW染毒后恢复2周),每组各取12只大鼠观察,雌雄各半。其中二氯甲烷染毒组大鼠每天经皮染毒6 h,每周5 d,连续4周。比较动物间体重、进食等一般状况的变化和试验期满血常规、血生化指标检测结果及主要脏器病理改变。结果试验期内雄鼠体重增长缓慢。血常规检测发现二氯甲烷染毒3.0和6.0 g/kg组雌鼠和1.5、3.0、6.0 g/kg组雄鼠淋巴细胞减少和中性粒细胞增多,与溶剂对照组比较差异有统计学意义(P<0.05)。染毒3.0和6.0 g/kg组雄鼠血清谷丙转氨酶和谷草转氨酶水平升高,6.0 g/kg组雄鼠血清甘油三酯含量降低,与溶剂对照组比较差异有统计学意义(P<0.05);而雌鼠未见明显异常。病理学结果显示大鼠染毒区皮肤表皮层和真皮层出现病变,肝细胞变性和坏死等病变,具有剂量-效应关系。恢复组大鼠在恢复期内血清生化指标和白细胞分类恢复正常,染毒区局部皮肤病变和肝细胞损害有一定程度改善,但未完全恢复。结论二氯甲烷28 d经皮肤重复剂量染毒可引起大鼠染毒区局部皮肤和肝细胞损伤,并伴随雄鼠体重、部分血常规及血清生化指标改变。
Objective To observe the toxicity of SD rats after transdermal administration of dichloromethane for 28 days. Methods One solvent control group (olive oil), four methylene chloride exposure groups (0.75, 1.5, 3.0 and 6.0 g / kg · BW) and one recovery group (6.0 g / kg · BW) Recovery for 2 weeks), 12 rats in each group were observed, male and female. The rats in the methylene chloride exposure group were transdermally treated for 6 hours a day for 5 days a week for 4 weeks. Comparison of animal weight, eating and other general conditions of change and test period of blood, blood biochemical indicators and major organs of the pathological changes. Results Male mice gained weight slowly during the trial period. The results of routine blood tests showed that there was significant difference between the control group and the solvent control group on the incidence of lymphocytosis and neutrophilia in the male mice exposed to dichloromethane at 3.0 and 6.0 g / kg and in the mice at 1.5, 3.0 and 6.0 g / kg (P <0.05). Serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels were increased in male and female rats exposed to 3.0 and 6.0 g / kg, serum triglyceride levels decreased in 6.0 g / kg male mice (P <0.05 vs. control group) ); No obvious abnormalities in female rats. Pathological results showed that there was a dose-response relationship between lesions and hepatocellular degeneration and necrosis in the epidermis and dermis of the exposed area of rats. In the recovery group, the serum biochemical indexes and leukocyte classification returned to normal in the recovery period. The local skin lesions and hepatocellular damage in the exposure area were improved to a certain extent, but not completely recovered. Conclusion Dopamine can cause local skin and hepatocyte injury in the exposed area of rats 28 d after repeated doses of the skin. The body weight, blood chemistry and serum biochemical indexes of the rats are also changed.