论文部分内容阅读
[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 effect of aluminum on the secretase mechanism of retinoic acid receptor α (RARα) and metalloproteinase-10 (α-ADAM10). [Method] Forty healthy male SD rats were randomly divided into four groups according to body weight: saline control, low dose (Al3 + 0.4 mg / kg · d) and middle dose (Al3 + 0.8 mg / kg · d) and high dose group (Al3 + 1.2 mg / kg · d), intraperitoneal injection of exposure, every 5 consecutive days, rest for 2 days, a total of 2 months. The rats were sacrificed and the cerebral cortex and hippocampus were removed and stored at -80 ° C. Aluminum content was determined by graphite furnace atomic absorption spectrometry. Western blot was used to detect the expression of RARα and α-ADAM10 secretase. [Results] The accumulation of aluminum in cerebral cortex and hippocampus of rats in each group increased significantly with the increase of exposure dose. Compared with 0.0 mg / kg group, the expression of α-ADAM10 in 0.4 mg / kg and above significantly increased (P <0.05), and there was a dose-effect relationship. Compared with 0.0 mg / kg group, the expression of RARα in the cortex induced by 0.4 mg / kg and above showed a significant downward trend (P <0.05) The expression level of RARα in the hippocampus was only 1.2 mg / kg, which was significantly lower than the other groups (P <0.05). [Conclusion] Aluminum can inhibit the expression of α-ADAM10 secretase and inhibit the expression of α-ADAM10 in brain by inhibiting the RARα pathway after aluminum sub-chronic exposure.