急性镉中毒的肝脏损伤机制及金属硫蛋白的保护作用

Mechanism of liver injury in cadmium toxication and protection of metallothionein

目的研究脂质过氧化和自由基在急性镉中毒性肝脏损伤中的作用及金属硫蛋白（ＭＴ）的保护作用。方法测定镉染毒后不同时间大鼠肝脏的ＭＴ和脂质过氧化产物丙二醛（ＭＤＡ）的含量及抗氧化酶的活力，观察肝细胞超微结构的损伤，进行自由基（Ｈ２Ｏ２）的定位。结果大鼠急性染镉后ＭＤＡ高于对照组（Ｐ＜０．０５）；抗氧化酶活力在３小时显著受抑（Ｐ＜０．０５），６小时明显恢复；ＭＴ在３小时即有增加，６小时达正常组的６．７倍；肝细胞膜上Ｈ２Ｏ２的阳性沉积物３小时最严重，２４小时已消失，但此时细胞损伤最严重，４８小时肝细胞再生、修复。结论镉可引起肝脏脂质过氧化及自由基的大量产生，抑制抗氧化酶的活力，造成细胞的严重损伤。ＭＴ对肝脏抗氧化酶活力的恢复、脂质过氧化的减轻、自由基的清除及损伤的肝细胞的保护可能有重要作用。

To study the mechanism of liver injury by lipid peroxidation and free radical and the protection of metallothionein(MT) in acute cadmium toxication,the contents of MT and malonyl dialdehyde(MDA),metabolic product of lipid peroxidation,and activities of antioxidases in cadmiumexposed rat liver at different time were determined.Meanwhile,the injury of hepatocytes and free radical(H2O2) localization were also studied by electron microscopy.The results showed that MDA content was increased(P<0.05) after acute cadmiumexposure,the activities of antioxidases significantly decreased(P<0.05) at 3 h and progressively recovered at 6 h.MT was increased at 3 h,reaching 6.7 times as much as that of control at 6 h.H2O2 positive precipitation on outer plasma membrane of hepatocytes was obviously increased at 3 h,and disappeared at 24 h but hepatocyte injury was very severe at this time,at 48 h hepatocyte recovered through regeneration.It is concluded that acute cadmium toxication would cause lipid peroxidation and excessive free radical production,and inhibit the activities of antioxidases leading to severe injury of hepatocytes.MT may have important role in the recovery of antioxidase activities alleviation of lipid peroxidation and elimination of free radicals,and protection from injury of hepatocytes.