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
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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& #183;d)、中剂量组(Al3+0.8 mg/kg& #183;d)和高剂量组(Al3+1.2 mg/kg& #183;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。 Abstract:Objective To explore the role of aluminum in the regulation of a 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+ 0.4 mg/kg& #183;d),mid-dose group(Al3+ 0.8 mg/kg& #183;d),and high-dose group(Al3+ 1.2 mg/kg& #183;d) by intraperitoneal 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 0.0mg/kg group,α-ADAM10 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 α-ADAM10 secrete enzymes expression through blocking RAR-α in rats with subchronic exposure to aluminum.
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