兴奋性氨基酸载体1和谷氨酸胱氨酸转运体在锰干扰谷胱甘肽合成中的作用

发布时间：2018-02-15 02:35

本文关键词： 锰谷胱甘肽兴奋性氨基酸载体谷氨酸胱氨酸转运体纹状体　出处：《环境与健康杂志》2015年08期 　论文类型：期刊论文

【摘要】：目的探讨兴奋性氨基酸载体1(EAAC1)和谷氨酸胱氨酸转运体(Xc-)在锰干扰谷胱甘肽(GSH)合成过程中的作用,为阐明锰中毒的发病机制和预防提供依据。方法清洁级昆明小鼠56只,雌雄各半,按体重随机分成4组(对照组及低、中、高剂量染锰组),每组14只。对照组腹腔注射0.9%氯化钠,低、中、高剂量染锰组的MnCl2染毒剂量分别为12.5、25、50 mg/kg,注射剂量均为5 ml/kg。每天染毒1次,持续2周。观察小鼠的一般形态及体重变化,HE染色观察脑纹状体的组织形态改变,FJC荧光染色观察纹状体内神经元退行性病变,试剂盒检测GSH含量,免疫组化法检测EAAC1和xCT的阳性表达,Western blotting法检测纹状体内EAAC1和xCT蛋白水平的变化。结果随着染锰剂量的增加,与对照组相比,小鼠精神状态先兴奋后逐渐倦怠,皮毛光泽逐渐减退且不整齐;同一时间的各组小鼠体重差异无统计学意义(P0.05)。25、50 mg/kg MnCl2组小鼠脑纹状体的组织形态损伤逐渐加重,神经元退行性病变进行性加重,细胞数目逐渐减少。与对照组相比,25、50 mg/kg MnCl2组小鼠脑纹状体内GSH含量降低,EAAC1和xCT的阳性表达和蛋白水平均下降,且50 mg/kg MnCl2组下降最明显,差异均有统计学意义(P0.05或P0.01)。结论过量的锰暴露可致小鼠脑纹状体内GSH合成障碍,其机制可能与EAAC1和xCT的调控障碍有关,从而对机体造成氧化损伤。
[Abstract]:Objective to investigate the role of excitatory amino acid vector (EAAC1) and glutamate cystine transporter (Xc-X) in the process of manganese interference in the synthesis of glutathione glutathione (GSH), and to provide a basis for elucidating the pathogenesis and prevention of manganese poisoning. Male and female were randomly divided into 4 groups according to their body weight (control group, low, medium and high dose manganese group, 14 rats in each group). The control group was intraperitoneally injected with 0.9% sodium chloride, low, medium, low, middle, low, low dose, low dose, low dose, low dose. In the high dose manganese group, the dose of MnCl2 was 12.5 渭 g / kg, and the dose was 5 ml / kg. For 2 weeks, the changes of general morphology and body weight of mice were observed. The histomorphology of striatum was observed by HE staining. The neurodegenerative lesions in striatum were observed by fluorescence staining. The content of GSH was detected by kit. Immunohistochemical method was used to detect the expression of EAAC1 and xCT. Western blotting was used to detect the changes of EAAC1 and xCT protein in striatum. Results with the increase of manganese concentration, compared with the control group, the mental state of mice was first excited and then gradually tired. There was no significant difference in body weight of each group of mice at the same time. The tissue morphological damage of striatum and neuronal degenerative lesion were gradually aggravated in the group of P0.05. 2550 mg/kg MnCl2, and the neurodegenerative lesion was gradually aggravated in the same time. Compared with the control group, the GSH content in the striatum of the mice in the 25 mg/kg group decreased the positive expression and protein levels of xCT and EAAC1, and the decrease in the 50 mg/kg MnCl2 group was the most obvious. Conclusion excessive manganese exposure can induce GSH synthesis disturbance in the striatum of mice, and its mechanism may be related to the regulation of EAAC1 and xCT, thus causing oxidative damage to the body.
【作者单位】：中国医科大学公共卫生学院环境卫生学教研室;
【基金】：国家自然科学基金(81302406)
【分类号】：R114

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