四硫钼酸盐对大鼠肠上皮细胞线粒体功能影响的研究

THE EFFECTS OF TETRATHIOMOLYBDATE ON INTESTINAL MITOCHONDRIA IN RATS

在体外试验中，四硫钼酸盐显著抑制上皮细胞氧消耗；抑制线粒体呼吸Ⅱ相（≥１ｍｍｏｌ／Ｌ）、Ⅲ相（≥０．２５ｍｍｏｌ／Ｌ）和解偶联呼吸（≥０．２５ｍｍｏｌ／Ｌ）；在≥１ｍｍｏｌ／Ｌ浓度作用２ｈ或４ｍｍｏｌ／Ｌ浓度作用１ｈ以上可轻度增加上皮细胞ＬＤＨ的释放，减慢线粒体在低渗ＮａＮＯ３和ＫＮＯ３溶液中的肿胀速度。体内试验表明，投服四硫钼酸盐（≥３３．

Tetrathiomolybdate has been described as a causative agent of secondary copper deficiency in ruminants It has since been used in the treatment of Wilsons disease In this study, tetrathiomolybdate was examined for its effect on the function of isolated cells and mitochondria from small intestinal epithelia For the in vitro studies,isolated epithelial cells and purified mitochondria were prepared and respiratory activities were measured Results showed that tetrathiomolybdate at the concentrations of higher than 0 05 mmol/L decreased the oxygen consumption of epithelial cells Respiration states 2 and 3,and uncoupled respiration of epithelial mitochondria were inhibited at the concentrations of 1,0 25 and 0 25 mmol/L,respectively Tetrathiomolybdate at the concentrations of higher than 1mmol/L for 2h ,or of 4mmol/L for longer than 1h increased LDH release from epithelial cells slightly The swelling of mitochondria in 0 1 mol/L sodium nitrate or potassium nitrate was reduced by tetrathiomolybdate For the in vivo studies,rats were intubated with 6 7,22,6 and 75 mg ammonia tetrathiomolybdate(10,33 3 & 111 mg Mo/kg BW) The intestinal epithelial mitochondria were isolated 24h after the intubation and cytochrome oxidase activities of the mitochondria were determined Decreases of the enzyme activities in rats treated with 33 3 and 111 mg Mo/kg BW were observed