中文摘要：

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。

英文摘要：

Objective To study the impact of the chronic aluminum exposure on Nmethyl-D-aspartate receptor 1（ NMDAR1） in the cortex and peripheral blood,and to explore the possibility that whether NMDAR1 of peripheral blood lymphocytes could be taken as a biomarker of aluminum exposure. Methods Thirty-two cleaning degree,healthy and male SD rats were randomly divided into four groups by weight,i. e. controlgroup,low-dose group,mid-dose group,and high-dose group separately. Different doses of Al Cl3（ 20,120 and 720 mg /kg） were added into the rats＇ drinking water,and control group was given tap water,each rat approximately drink 10 m L /100 g,the experiment lasted 360 days. Then,plasma aluminum and cortex aluminum were measured by atom absorption spectrometry with graphite furnace（ GFAAS）,relative expression of NMDAR1 gene was assayed by real-time fluorescence quantitative polymerase chain reaction（ RTPCR） and NMDAR1 protein both in the cortex and peripheral blood lymphocytes were assayed by enzyme-linked immunosorbent（ ELISA）. Results Plasma aluminum increased with the increase of Al exposure dose（ P 0. 05）,the result of plasma aluminum were69. 88,83. 10,87. 06 and 134. 60 μg / L,respectively,plasma aluminum in low-dose,mid-dose and high-dose group were significant increased,compared to the control group.Cortex aluminum increased with the increasing of aluminum dose（ P 0. 05）,the result of cortex aluminum were 0. 065,0. 102,0. 139 and 0. 228 μg / mg,respectively. The differences among groups were significant（ P 0. 05）. The expression of NMDAR1 gene both in the cortex and peripheral blood lymphocytes were reduced with the increasing of aluminum dose（ P 0. 05）. The differences of gene expression in the cortex among the three groups were significant statistically（ P 0. 05）. The differences of gene expression in peripheral blood lymphocytes among the three groups were significant statistically（ P 0. 05）,but there was no significantly statistical difference between mid- and high-dos