中文摘要：

目的观察氯化铝（AlCl3）对大鼠海马淀粉样前体蛋白（APP）启动子区甲基化及β淀粉样蛋白（Aβ）含量的影响。方法健康6月龄雄性SPF级SD大鼠40只,分成4组（正常对照组和AlCl3低、中、高剂量组）,每组10只,各组分别腹腔注射AlCl30、10、20和30 mg/kg组,正常对照组注射相应体积生理盐水,连续5天,休息2天,共8周。甲基化特异性PCR法（MSP）检测海马APP启动子区的甲基化状态,实时荧光定量PCR（RT-PCR）测定APP mRNA表达水平,ELISA法测APP、Aβ（42）蛋白表达量。结果随着AlCl3浓度的增加,大鼠平均逃避潜伏期明显延长（P〈0.05）,AlCl3中、高剂量组穿越平台的次数明显减少（P〈0.05）;AlCl3染毒组海马APP启动子区甲基化检出率降低（χ^2=27.61,P〈0.05）,其中,高剂量组APP甲基化的检出率低于其余3组（P〈0.01）,APP甲基化的检出率随AlCl3染毒剂量增加而降低的趋势（趋势χ^2=19.08,P〈0.01）。各AlCl3染毒组APP mRNA的表达水平高于生理盐水组（F=8.973,P〈0.05）。与正常对照组比较,各AlCl3染毒组大鼠海马APP、Aβ（42）蛋白浓度均增高（F=11.14,P=0.032;F=17.82,P=0.018）。与低剂量组相比,中剂量组APP蛋白表达量增加,高剂量组APP、Aβ（42）蛋白表达量增加,差异均有统计学意义（P〈0.05）。Aβ（42）蛋白免疫组化法检测结果示,中、高剂量组海马神经细胞内外出现棕黄色物质,考虑有Aβ的沉积。结论氯化铝染毒可引起大鼠海马APP启动子甲基化水平降低,进而影响APP mRNA表达水平增高,海马组织APP表达量增多,从而导致Aβ产生增多而沉积。

英文摘要：

Objective To study the effect of aluminum chloride on amyloid precursor protein（ APP） promoter methylation and the content of amyloid β-protein（ Aβ） in hippocampus of rats. Methods Forty male SPF grade SD rats were divided into four groups： control group（0.9% NaCl）,10 mg / kg AlCl3 group,20 mg / kg AlCl3 group,and 30 mg / kg AlCl3 group,respectively. After treatment for 8 weeks,the APP methylation level and expressions of APP mRNA was detected by methylation specific PCR and quantitative real time PCR,respectively. The content of APP and Aβ were detected with enzym-linked immunosorbent assay（ ELISA）. Results With the increase of the content of aluminium chloride,the escape latency were significantly prolong（ P〈0. 05）,numbers of traversing flat in AlCl320 mg / kg and AlCl330 mg / kg group high and were significantly decreased（ P〈0. 05）,the methylation level of APP contaminated by AlCl3 were decreased（ χ^2= 27. 61,P〈0. 05）,the level of APP methylation in 30 mg / kg AlCl3 group was lower than three groups（ P〈0. 01）. With the increase of aluminium chloride,the level of APP methylation were decreased（ χ^2= 19. 08,P〈0. 01）. With the increase of the content of aluminium chloride,the methylation level of APP treated with 20 mg / kg AlCl3and30 mg / kg AlCl3 were decreased compared with control group（ P〈0. 05）,the level of APP methylation in 30 mg / kg AlCl3 group was lower than 10 mg / kg AlCl3 group（ P〈0. 05）,the APP mRNA expression level in AlCl3 group was of statistical significance compared to the control group（ F = 8. 973,P〈0. 05）,the level of APP mRNA in 30 mg / kg AlCl3 were higher than 10 mg / kg AlCl3（ P〈0. 05）. Compared with the control group,the content of APP and Aβ in hippocampus of AlCl3 group were increased（ F = 11. 14,P = 0. 032,F =17. 82,P = 0. 018）,and 30 mg / kg AlCl3 group were higher than 10 mg / kg AlCl3（ P〈0. 05）,the content of APP in 20 mg / kg AlCl3 group were higher than 10 mg / kg AlCl3（ P〈0. 05）. The r