Objective: To investigate the influence of aluminum on microRNA29 (miR29) subtypes miR29a, miR29a*, miR29b1, miR29b2, miR29c1, and miR29c2 and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in the brain of rats. Methods: A total of 40 Sprague-Dawley rats were randomly divided into control group and 15, 30, and 45 μmol/kg groups according to the body weight, with 10 rats in each group. The rats were exposed to aluminum (at a dose of 0.1 ml/100 g body weight) by intraperitoneal injection for 8 weeks. The rats in control group were given 0.9% normal saline, and those in exposure groups were given aluminum-maltolate (equivalent volumesof maltolate and aluminum solution were mixed before exposure) . The cerebral cortex and hippocampus were isolated after exposure ended; Western blotting was used to measure the change in BACE1 expression, and real-time reverse transcription polymerase chain reaction was used to measure the mRNA expression of miR29 subtypes in the cerebral cortex and hippocampus. Results: Compared with the control group, the 45 μmol/kg group had a significant increase in BACE1 expression in the cerebral cortex, and the 30 and 45 μmol/kg groups had significant increases in BACE1 expression in the hippocampus (all P<0.05) . Compared with the control group, the 15, 30, and 45 μmol/kg groups had significant reductions in the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 in the cerebral cortex and hippocampus (all P<0.01) , and the 45 μmol/kg group had significant reductions in the mRNA expression of miR29a and miR29b1 in the cerebral cortex and hippocampus (all P<0.05) . The results of correlation analysis showed that there was no correlation between the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 and BACE1 expression in the cerebral cortex and hippocampus (all P>0.05) , while the mRNA expression of miR29a and miR29b1 was negatively correlated with BACE1 expression (cerebral cortex: r=-0.987 and -0.981, P<0.05; hippocampus: r=-0.992 and -0.991, P<0.05) . Conclusion: Aluminum can reduce the expression of miR29 subtypes and increase BACE1 expression in the brain, and the expression of miR29a and miR29b1 is negatively correlated with BACE1 expression.
目的： 研究铝对大鼠脑内微小核糖核酸29（miR29）各亚型（miR29a、miR29a*、miR29b1、miR29b2、miR29c1、miR29c2）及β淀粉样前体蛋白裂解酶1（BACE1）的影响情况。 方法： 40只普通级SD大鼠按体重随机分为对照组和15、30、45 μmol/kg组，每组10只。采用腹腔注射的方式染毒（注射量为0.1 ml/100 g体重）8周，对照组给予0.9%生理盐水，染毒组给予不同浓度的麦芽酚铝（染毒前将麦芽酚和铝溶液等体积混合）。染毒结束后，分离大鼠脑皮质和海马，采用蛋白免疫印迹（Western blotting）法检测BACE1蛋白的变化；实时荧光定量反转录聚合酶链反应（RT-PCR）检测大鼠脑皮质和海马miR29各亚型基因的表达水平。 结果： 与对照组比较，45 μmol/kg组大鼠脑皮质BACE1蛋白表达明显升高，30、45 μmol/kg组大鼠海马BACE1蛋白表达明显升高，差异均有统计学意义（均P<0.05）；与对照组比较，15、30、45 μmol/kg组大鼠脑皮质和海马中miR29a*、miR29b2、miR29c1、miR29c2基因表达明显降低，差异均有统计学意义（均P<0.01）；与对照组比较，45 μmol/kg组大鼠脑皮质和海马miR29a和miR29b1基因表达明显降低，差异均有统计学意义（均P<0.05）。相关分析结果显示，皮质和海马miR29a*、miR29b2、miR29c1、miR29c2基因与BACE1蛋白表达均无相关性（均P>0.05），而miR29a、miR29b1基因与BACE1蛋白表达均呈负相关（皮质：r=-0.987、-0.981；海马：r=-0.992、-0.991；均P<0.05）。 结论： 铝可以引起脑内miR29各亚型表达降低，BACE1表达升高，且miR29a、miR29b1与BACE1表达呈负相关。.
Keywords: Aluminum; BACE1; Rats; miR29.