亚慢性染砷对小鼠脑组织线粒体琥珀酸脱氢酶活性及蛋白表达的影响

Effect of subacute arsenic exposure on activity and expression of mitochondrial SDH in brain of mice

目的观察砷对小鼠脑组织线粒体琥珀酸脱氢酶(SDH)活性及其α亚单位(Sdha)蛋白表达的影响,以及牛磺酸和维生素C对上述影响的干预作用,为探讨砷的神经毒作用机制提供分子毒理学依据。方法SPF级小鼠50只,按体重将小鼠随机分为1 ppm三氧化二砷(As2O3)染毒组、4 ppm As2O3染毒组、牛磺酸抗氧化干预组(4ppm As2O3+150 mg/kg牛磺酸)、维生素C抗氧化干预组(4 ppm As2O3+45 mg/kg维生素C)和对照组。通过自然饮用含不同浓度As2O3蒸馏水的方式使小鼠染毒;干预剂以灌胃方式投给,每星期2次,连续染毒60 d。于染毒第0天、15天、30天、60天时取脑,提取脑组织线粒体,检测SDH的活性和Sdha蛋白表达。结果在染砷第60天,染砷组小鼠脑组织线粒体SDH活性和Sdha蛋白表达量均下降,尤其4 ppm染砷组小鼠脑组织线粒体的SDH活性和Sdha蛋白表达量都明显低于对照组(P<0.05);而牛磺酸和维生素C干预组,小鼠脑组织线粒体SDH活性和Sdha蛋白表达量均显著高于4 ppm染砷组。其中砷暴露后第30天和第60天的小鼠脑组织线粒体SDH活性和Sdha蛋白表达量均显著低于染砷0天(P<0.05)。结论亚慢性砷暴露能导致脑组织线粒体SDH的活性降低和Sdha蛋白表达下调,而牛磺酸和维生素C对砷导致的SDH毒性可能具有一定的拮抗作用。

Objective To explore the effect of subacute arsenic exposure on the activity of mitochondrial succinate dehydrogenase （SDH） and expression of its subunit A （Sdha） protein in brain of mice and the protective effects of taurine and vitamin C. Methods 50 mice were randomly divided into 5 groups, group 1 were only given drinking water （ control group） ; group 2 and 3 were treated with 1 or 4 mg/L arsenic trioxide, respectively; mice in group 4 and 5 were administered with 4 mg/L arsenic trioxide and 150 mg/kg tanrine or 45 mg/kg Vit C, respectively. Arsenic trioxide was dissolved into drinking water, tanrine and Vit C were given by gavage twice a week, experimental period was 60 days. At the 0, 15th, 30th and 60th day after exposure, mice were killed by decapitation and their brains were taken. For the detection of the activities of mitochondrial SDH and expression levels of Sdha protein. Results The activities of SDH and levels of Sdha protein in mitochondria of brain were all decreased at the 60th day after As exposure, especially the group 4 which received 4 mg/L As2O3 （P 〈0. 05） ; while the activities of SDH and expression of Sdha protein in protective groups were significantly higher than those received 4 mg/L As2 O3 administration （ P 〈 0. 05 ）. In the group 4 （ received 4 mg/L As3 O3 ）, the activities of SDH and expression of Sdha protein at 30th or 60th day after exposure were also significantly lower than those at the 0 day of exposure （ P 〈 0. 05 ）. Conclusions The results showed that subacute arsenic exposure can induce the inhibition of the activities of SDH and the expression of Sdha protein in mitochondria of brain, while taurine and Vit C seem to have some antagonistic effect on these toxic effects of As.