金属硫蛋白对镍致小鼠肝损伤的保护作用

Protection from Nickel-induced Liver Injury by Metallothionein in Mice

目的探讨金属硫蛋白对镍致小鼠肝损伤的保护作用及其机制。方法利用硫酸镍染毒复制小鼠肝损伤的模型,然后腹腔注射不同剂量的金属硫蛋白7 d,检测肝脏器系数、肝功能及肝组织脂质过氧化等指标,并行肝组织病理学观察。结果肝损伤模型组与金属硫蛋白(MT)保护组小鼠肝脏器系数差异有统计学意义(P<0.05),随着MT剂量的增加,肝脏器系数逐渐降低(P<0.05);MT保护组肝细胞炎性浸润、水肿及坏死明显减轻,肝窦结构有恢复;MT保护组小鼠血清AST、ALT、GGT及总胆汁酸均低于损伤模型组(P<0.05),肝组织MDA、GSH低于损伤模型组(P<0.05),而SOD、GSH-Px活性则高于损伤模型组(P<0.05),并均有较强的剂量依赖关系。结论金属硫蛋白对镍致小鼠肝损伤有保护作用,保护机制可能与减轻氧化损伤有关。

Objective To explore the protection of metallothionein against liver injury induced by nickel in mice and its mechanisms. Methods Different doses of metallothionein were intraperitoneally injected to mice with nickel sulfate- induced liver injury for 7 days. The liver organ coefficient, liver function and liver lipid peroxidation were detected. The pathological changes in the liver ti^ue were observed. Results The liver organ coefficient was statistically different between the liver inju- ry model group and the metallothionein protection groups （P （0.05）, and with the increase of the metallothionein dose, the liver organ coefficient decreased. In the metallothionein protection groups, the hepatic cellular inflammatory infiltration, edema and necrosis were obviously alleviated, and the hepatic sinusoid structure was partly recovered. The serum aspartate aminotransferase （AS＇T）, alanine aminotransferase（ALT）, gamma glutamyltransferase （CK3T） and total bile acid（TBA） in the metallothionein protection groups were significantly lower than those in the liver injury model group（P 〈 0.05）. So were the MDA and GSH con- tents in the liver tissue （P〈O. 05）. But the SOD and GSH- Px activities in the liver tissue were statistically higher （P〈0.05）. The indicators changed in a dose - dependent manner. Conclusions Metallothionein can protect mice from liver injury in- duced by nickel, and the protective mechanism may involve alleviating the oxidative damage.