亚慢性铝暴露对大鼠脑内视黄酸受体α调节解聚素和金属蛋白酶-10分泌酶的影响  

Effects of Subchronic Exposure to Aluminum on Retinoic Acid Receptors–α Regulation of a Disintegrin and Metalloproteinase-10 in Rat Brain

作　　者：胡佳丽[1] 王林平[1] 牛侨[1] 

机构地区：[1]山西医科大学公共卫生学院劳动卫生教研室,山西030001

出　　处：《环境与职业医学》2014年第3期176-179,共4页Journal of Environmental and Occupational Medicine

基　　金：阿尔兹海默病动物模型的基因治疗及试剂盒的开发(编号:2011-重点3)

摘　　要：[目的]探索铝对视黄酸受体α(RARα)调节解聚素和金属蛋白酶-10(α-ADAM10)分泌酶机制的影响。[方法]取40只健康雄性SD大鼠,按体质量随机分为4组:溶剂对照(生理盐水)、低剂量组(Al3+0.4 mg/kg·d)、中剂量组(Al3+0.8 mg/kg·d)和高剂量组(Al3+1.2 mg/kg·d),腹腔注射染毒,每连续5 d,休息2 d,共2月。处死大鼠,分别取大脑皮质和海马,保存于-80℃。采用石墨炉原子吸收法检测各组铝含量,Western blot法检测RARα和α-ADAM10分泌酶的表达。[结果]随着染毒剂量的增加,各组大鼠脑皮质、海马中铝的蓄积量均明显上升;与0.0 mg/kg组相比,0.4 mg/kg及以上浓度致α-ADAM10表达明显下降(P<0.05),呈剂量-效应关系;与0.0 mg/kg组相比,0.4 mg/kg及以上浓度致皮质RARα表达呈明显下降趋势(P<0.05)且呈剂量-效应关系,而海马RARα表达仅1.2 mg/kg剂量组明显低于其他组且有统计学差异(P<0.05)。[结论]大鼠经铝亚慢性染毒后,铝可能通过抑制RARα途径,从而进一步使α-ADAM10分泌酶受到抑制,影响其在脑内的表达。[ Objective ] To explore the role of aluminum in the regulation ofa disintegrin and metalloproteinase-10 （α-ADAM10） via retinoic acid receptors-α（RAR-α. [ Methods ] Healthy male SD rats （n=40） were randomly divided by weight into four groups： control group （saline）, low-dose group （Al3. 0.4mg/kg . d）, mid-dose group （Al3＋ 0.8 mg/kg . d）, and high-dose group （Al3. 1.2 mg/kg . d） by iutraperitoneal injection for five consecutive days per week in a period of two months. Rats were neutralized at the end of the two-month exposure, and cerebral cortex and hippocampus samples were dissected from each rat and stored at -80℃. Graphite furnace atomic absorption spectrometry was used to detect aluminum content. Western blot was used to determine the expressions of RAR-α and α-ADAM10. [ Results ] With the exposure dose increasing, the aluminum contents in cerebral cortex and hippocampus were significantly increased. Compared with the 0.0 mg/kg group, α-ADAM 10 expression was significantly decreased in the 0.4 mg/kg and above groups in a dose-response manner （P 〈 0.05）. A decreasing trend was also observed for RAR-α expression in cerebral cortex in the groups treated with 0.4 mg/kg and more in a dose-response manner （P〈 0.05）, while only the 1.2 mg/kg group showed a significant decrease in RAR-α expression in hippocampus compared with the other groups （P 〈 0.05）. [ Conclusion ] Aluminum may inhibit a-ADAM 10 secrete enzymes expression through blocking RAR-α in rats with subchronic exposure to aluminum.

关 键 词：麦芽酚铝 视黄酸受体α 解聚素和金属蛋白酶-10 皮质 海马 亚慢性染毒 

分 类 号：R114[医药卫生—卫生毒理学]