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目的研究慢性铝暴露对脑皮质与外周血淋巴细胞N-甲基-D-天冬氨酸受体1(NMDAR1)的影响,探讨外周血淋巴细胞NMDAR1作为外周血中铝暴露生物标志物的可能性。方法选取2月龄健康雄性清洁级SD大鼠32只,按体重随机分为空白组和铝低、中、高剂量组,空白组饮用自来水,铝低、中、高剂量组分别给予20、120、720 mg/L Al Cl3饮水,大鼠每日饮水约10 m L/100 g,连续染毒360 d。染毒结束,采用石墨炉原子吸收法测定血浆铝和脑铝含量,采用实时荧光定量聚合酶链反应法(RT-PCR)测定脑皮质与外周血淋巴细胞中NMDAR1基因相对表达量,酶联免疫吸附法(ELISA)测定脑皮质和外周血淋巴细胞中NMDAR1蛋白含量。结果对照组及铝低、中、高剂量组血浆铝含量分别为69.88、83.10、87.06和134.60μg/L,铝低、中、高剂量组高于对照组,差异有统计学意义(P<0.05);脑铝含量分别为0.065、0.102、0.139和0.228μg/mg,铝低、中、高剂量组高于对照组,差异有统计学意义(P<0.05)。NMDAR1基因表达随铝剂量升高呈下降趋势,脑皮质基因相对表达量铝中、高剂量组低于对照组(P<0.05);外周血淋巴细胞NMDAR1基因表达铝中、高剂量组低于铝低剂量组和对照组(P<0.05),铝中、高剂量组之间比较差异无统计学意义(P=0.167)。脑皮质NMDAR1蛋白含量铝高剂量组低于对照组、铝低剂量组(P<0.05);铝中剂量组低于对照组(P<0.05);淋巴细胞NMDAR1蛋白含量铝高剂量组低于对照组、铝低剂量组(P<0.05),与铝中剂量组比较差异无统计学意义(P=0.159)。结论慢性铝暴露可影响大鼠脑皮质与外周血淋巴细胞NMDAR1基因相对表达量和蛋白表达,随铝剂量的增加基因相对表达量和蛋白表达下降,可将NMDAR1作为铝暴露外周生物标志物进一步研究。
Objective To investigate the effect of chronic aluminum exposure on N-methyl-D-aspartate receptor 1 (NMDAR1) in cerebral cortex and peripheral blood lymphocytes and explore the possible role of peripheral blood lymphocyte NMDAR1 as biomarker of aluminum exposure in peripheral blood Sex. Methods Thirty-two healthy male SD rats of 2 months old were randomly divided into blank group and aluminum low, medium and high dose groups according to body weight. Drinking water was used in the blank group, while low, medium and high dose aluminum groups were given 20,120 , 720 mg / L Al Cl3 drinking water, rats daily drinking water about 10 m L / 100 g, continuous exposure 360 d. At the end of exposure, the contents of aluminum and brain aluminum in plasma were determined by graphite furnace atomic absorption spectrometry. The relative expression of NMDAR1 in cerebral cortex and peripheral blood lymphocytes was determined by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) The content of NMDAR1 protein in cerebral cortex and peripheral blood lymphocytes was determined by ELISA. Results The contents of aluminum in the control group and aluminum low, middle and high dose groups were 69.88, 83.10, 87.06 and 134.60 μg / L, respectively. The levels of aluminum in low, middle and high dose aluminum groups were significantly higher than those in the control group (P <0.05 ). The content of brain aluminum was 0.065,0.102,0.139 and 0.228μg / mg, respectively. The levels of aluminum in the low, middle and high dose groups were higher than those in the control group (P <0.05). The expression of NMDAR1 gene was decreased with the increase of aluminum dose. The relative expression of cortical gene in aluminum medium and high dose group was lower than that in control group (P <0.05). NMDAR1 gene expression in peripheral blood lymphocytes was lower than that of aluminum Low dose group and control group (P <0.05). There was no significant difference between the medium and high dose aluminum groups (P = 0.167). The content of NMDAR1 protein in the cerebral cortex was lower in the aluminum high-dose group than in the control group and the aluminum low-dose group (P <0.05), while the middle aluminum dose group was lower than the control group (P <0.05) Group and aluminum low dose group (P <0.05), but there was no significant difference compared with aluminum medium dose group (P = 0.159). Conclusion Chronic aluminum exposure can affect the expression of NMDAR1 mRNA and protein in rat cerebral cortex and peripheral blood lymphocytes. NMDAR1 can be used as a peripheral biomarker of aluminum exposure with the increase of aluminum dose, and the decreased expression of protein and protein .