杨天瑶, 徐兆发, 刘巍, 魏衍刚, 邓宇, 徐斌. α-硫辛酸对甲基汞致大鼠脑谷氨酸代谢转运障碍的拮抗作用[J]. 环境与职业医学, 2013, 30(10): 770-773.
引用本文: 杨天瑶, 徐兆发, 刘巍, 魏衍刚, 邓宇, 徐斌. α-硫辛酸对甲基汞致大鼠脑谷氨酸代谢转运障碍的拮抗作用[J]. 环境与职业医学, 2013, 30(10): 770-773.
YANG Tian-yao , XU Zhao-fa , LIU Wei , WEI Yan-gang , DENG Yu , XU Bin . Antagonistic Effect of α-Lipoic Acid on Disruptions of Glutamate Metabolism and Transport Induced by Methylmercury in Rat Brain[J]. Journal of Environmental and Occupational Medicine, 2013, 30(10): 770-773.
Citation: YANG Tian-yao , XU Zhao-fa , LIU Wei , WEI Yan-gang , DENG Yu , XU Bin . Antagonistic Effect of α-Lipoic Acid on Disruptions of Glutamate Metabolism and Transport Induced by Methylmercury in Rat Brain[J]. Journal of Environmental and Occupational Medicine, 2013, 30(10): 770-773.

α-硫辛酸对甲基汞致大鼠脑谷氨酸代谢转运障碍的拮抗作用

Antagonistic Effect of α-Lipoic Acid on Disruptions of Glutamate Metabolism and Transport Induced by Methylmercury in Rat Brain

  • 摘要: 目的 探讨α-硫辛酸(alpha-lipoic acid,α-LA)对甲基汞所致大鼠脑谷氨酸代谢转运障碍的拮抗作用。

    方法 清洁级Wistar 大鼠24 只,按体重随机分为4 组,分别为对照组,低、高甲基汞染毒组和α-LA干预组,每组6 只,雌雄各半。对照组和低、高甲基汞染毒组先皮下注射0.9%氯化钠溶液,α-LA干预组皮下注射35 μmol/kg α-LA;2 h 后,对照组腹腔注射0.9%氯化钠溶液,低、高甲基汞染毒组和α-LA干预组分别腹腔注射氯化甲基汞4、12 和12 μmol/kg。α-LA预处理隔日1 次;染毒组每日1 次,每周5 次;连续处理4 周。最后1 次染毒24 h 后,分离大鼠大脑皮质,制备5%、10%的组织匀浆,测定大脑皮质汞(Hg)、谷氨酸(Glu)、谷氨酰胺(Gln)含量,及谷氨酰胺酶(PAG)、谷氨酰胺合成酶(GS)、Na+-K+-ATPase、Ca2+-ATPase 活力。

    结果 甲基汞高剂量染毒组大鼠脑汞为(17.72& #177;1.36)μg/g组织、Glu 含量为(71.57& #177;10.87)μmol/g蛋白、PAG活力为(31.26& #177;4.38)μmol/(min& #183;g蛋白),均高于对照组(P<0.01);Gln含量及GS活力分别为(0.15& #177;0.04)μmol/g蛋白及(23.89& #177;3.60)U/g蛋白,Na+-K+-ATPase 及Ca2+-ATPase 活力分别为(4.03& #177;0.57)μmol/(mg蛋白& #183;h)及(2.21& #177;0.62)μmol/(mg 蛋白& #183;h),均低于对照组(P<0.01);与甲基汞高剂量染毒组比较,α-LA干预组大鼠脑汞含量未见明显变化;Glu 含量(63.02& #177;3.33)μmol/g 蛋白及PAG 活力(26.03& #177;3.88)μmol/(min& #183;g 蛋白)均降低(P<0.01 或P<0.05),Gln含量(0.20& #177;0.05)μmol/g 蛋白、GS 活力(34.05& #177;4.23)U/g 蛋白、Na+-K+-ATPase 活力为(5.52& #177;1.16)μmol/(h& #183;mg 蛋白)及Ca2+-ATPase 活力为(3.27& #177;0.60)μmol/(h& #183;mg 蛋白),均升高(P<0.01 或P<0.05)。

    结论 α-LA对甲基汞所致大鼠脑谷氨酸代谢紊乱有一定的拮抗作用。

     

    Abstract: Objective To probe the antagonistic effect of alpha lipoic acid (α-LA) on the glutamate metabolism and transport disrupted by methylmercury.

    Methods Twenty-four Wistar rats were randomly divided into 4 groups by weight (6 rats per group including 3 male and 3 female):a control group, a low-and a high-dose methylmercury groups, and an α-LA pretreatment group. The control and the methylmercury groups were treated by subcutaneous injection with 0.9% NaCl, and the pretreatment group was injected with 35 μmol/kg α-LA. Two hours later, the control group was peritoneally injected with 0.9% NaCl; the two methylmercury groups and the pretreatment group were peritoneally injected with 4, 12, and 12 μmol/kg CH3HgCl, respectively. The administration frequency of CH3HgCl was every 2 days for the α-LA pretreatment group, and every day (that was 5 times/week) for the two methylmercury groups. The administration protocol lasted for 4 weeks. Twenty-four hours after the last administration, the cerebral cortex was harvested to prepare 5% and 10% homogenates; the concentrations of Hg, Glu, Gln, as well as the activity of phosphate activated glutaminase (PAG), glutamine synthetase (GS), Na+-K+-ATPase, and Ca2+-ATPase were determined.

    Results In comparison with the control group, the concentrations of mercury(17.72& #177;1.36) μg/g tissue, Glu(71.57& #177;10.87) μmol/g protein, and the PAG activity(31.26& #177;4.38) μmol/(min& #183;g protein) in the brain tissue of high-dose methylmercury treated rats were significantly increased (P< 0.01); the concentration of Gln(0.15& #177;0.04) μmol/g protein and the GS activity(23.89& #177;3.60) U/g protein were significantly decreased (P< 0.01); the activities of Na+-K+-ATPase(4.03& #177;0.57) μmol/(h& #183;mg protein) and Ca2+-ATPase(2.21& #177;0.62) μmol/(h& #183;mg protein) were significantly lowered (P< 0.01). The above-mentioned indicators' alterations were smaller in the α-LA treated group:the concentrations of Glu(63.02& #177;3.33) μmol/g protein and Gln(0.20& #177;0.05) μmol/g protein; activities of PAG(26.03& #177;3.88) μmol/(min& #183;g protein), GS(34.05& #177;4.23) U/g protein, Na+-K+-ATPase(5.52& #177;1.16) μmol/(h& #183;mg protein),and Ca2+-ATPase(3.27& #177;0.60) μmol/(h& #183;mg protein). The differences of the above indicators between the α-LA treated group and the high-dose methylmercury group showed statistical significance (P< 0.01 or P< 0.05).

    Conclusion α-LA can serve as a protective agent against glutamate metabolism disrupted by methylmercury.

     

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