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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 observe the effect of arsenic on the activity of mitochondrial succinate dehydrogenase (SDH) and the expression of α-subunit (Sdha) protein in brain tissue of mice and the effect of taurine and vitamin C on the above effects. Toxicity mechanisms provide molecular basis for toxicology. Methods Fifty SPF mice were randomly divided into 1 ppm arsenic trioxide (As 2 O 3) group, 4 ppm As 2 O 3 poisoning group, and 4 mg of As 2 O 3 + 150 mg / kg taurine Acid), vitamin C antioxidant intervention group (4 ppm As2O3 + 45 mg / kg vitamin C) and control group. The mice were exposed to natural drinking water containing different concentrations of As2O3. The interventional agents were administered intragastrically twice a week for 60 days. The brain was taken at 0, 15, 30 and 60 days after exposure. The mitochondria of brain tissue were extracted and the activity of SDH and the expression of Sdha protein were detected. Results On the 60th day after arsenic exposure, the mitochondrial SDH activity and the expression of Sdha protein in brain tissue of arsenic-treated mice decreased. Especially, the mitochondria SDH activity and Sdha protein expression in brain of 4 ppm Arsenite-treated mice were significantly lower than those of control (P <0.05). However, SDH activity and Sdha protein expression in mitochondria of mice treated with taurine and vitamin C were significantly higher than those exposed to 4 ppm arsenic. The mitochondrial SDH activity and Sdha protein expression in brain tissue of mice on the 30th and the 60th day after arsenic exposure were significantly lower than those of the arsenic-treated day 0 (P <0.05). Conclusion Subchronic exposure to arsenic causes a decrease in mitochondrial SDH activity and down-regulation of Sdha protein in brain tissue, whereas taurine and vitamin C may have antagonistic effects on arsenic-induced SDH toxicity.