镍铬钴混合物对小鼠肝脏毒作用机制的研究

Study on mechanism of liver toxicity of mixture of nickel sulfate,potassium dichromate and cobalt chloride in mice

目的 探讨镍铬钴混合物致小鼠肝脏损伤的机制 ,为早期防治镍铬钴混合物联合毒性所致的肝脏损伤提供理论依据。方法 模拟金川矿区矿石中Ni、Cr、Co平均含量百分比 (0 2 6∶0 3 0∶0 0 2 ) ,连续 10d小鼠腹腔注射硫酸镍 2 5mg/kg、重铬酸钾 0 14mg/kg、氯化钴 0 41mg/kg及混合物 0 0 9,0 17mg/kg染毒。制备肝细胞膜 ,采用定磷比色法检测肝细胞膜Ca2 + -ATPase活性 ;PDE法检测钙调素 (CaM)含量 ;TBA法检测MDA含量和邻苯三酚自氧化改进法测定SOD活性。结果 各单体和混合物明显抑制肝细胞膜Ca2 + -ATPase活性 ,使肝组织中钙调素 (CaM )含量降低 ,MDA含量升高的同时抑制SOD活性 ,尤以混合物组显著 ,并且混合物毒性大于各单体毒作用。结论 混合物在体内可能产生联合毒性 ,抑制肝细胞膜Ca2 + -ATPase活性 ,使钙调素 (CaM)含量降低 ,导致钙稳态失衡 ;

Objective To study the mechanism of NiSO 4,K 2CrO 7,CoCl 2 and the mixture to damage liver of mice in order to provide theoretical evidence for preventing and curing joint toxicity of the mixture.Methods Several groups of mice were exposed respectively to NiSO 4,K 2Cr 2O 7,CoCl 2 at dose of 2.5,0.14,0.41 mg/kg and a mixture of them at 0 09,0.17 mg/kg according to the ores percentage of average content(Ni∶Cr∶Co=0 26∶0 30∶0 02) in the Jinchuan area through intraperitoneal injection for 10 days.Liver cell spare slurry and cell membrane were prepared to assess the activity of Ca 2+ -ATP ase ,CaM,MDA and SOD with enzyme and biochemical assay.Results The enzyme activity of Ca 2+ -ATP ase and SOD were inhabited and the content of CaM decreased and meanwhile MDA was increased by NiSO 4,K 2Cr 2O 7,CoCl 2 and the mixture.In addition,the mixture toxicity were stronger than that of NiSO 4,K 2Cr 2O 7,CoCl 2 lonely.Conclusion The mixture could cause joint toxicity in the body of mice and inhabit the activity of Ca 2+ -ATP ase and decrease the content of CaM and increase the peroxidation function of liver cell membrane so as to damage the liver.However,the mechanism of joint toxicity on the mixture should be studied further.