γ-分泌酶在铝致大鼠脑内Aβ蓄积中作用  

Role of γ-secretase during accumulation of Aβ induced by aluminum in rat's brain

作　　者：王林平[1] 王静 石樱桃[3] 张玲[1] 牛侨[1] 

机构地区：[1]山西医科大学公共卫生学院,山西太原030001 [2]中国石油集团石油职业卫生技术服务中心 [3]山西省肿瘤医院

出　　处：《中国公共卫生》2013年第11期1632-1634,共3页Chinese Journal of Public Health

摘　　要：目的探讨γ-分泌酶在铝引起脑内β-淀粉样蛋白(Aβ)蓄积中的作用。方法 32只SD大鼠随机分为对照组,麦芽酚铝低、中、高剂量组(0.4、0.8、1.2 mg/kg);腹腔注射麦芽酚铝8周后,酶联免疫吸附试验和western-blot检测大鼠皮质和海马Aβ的量和γ-分泌酶组成亚单位早老素1(presenilin 1)和nicastrin蛋白。结果在皮质内,高剂量染铝组Aβ总量为(120.58±23.65)pg/mL,在海马内中、高剂量染铝组Aβ总量为(115.57±7.00)、(127.09±11.04)pg/mL,均高于对照组(P<0.05);在皮质和海马内,与对照组比较,各染毒组Aβ40无明显变化;在皮质内,高剂量染铝组Aβ42为(51.02±20.90)pg/mL,在海马内,低、中、高剂量染铝组Aβ42分别为(24.84±5.05)、(42.52±12.13)、(54.42±7.98)pg/mL,均高于对照组(P<0.05);与对照组比较,中、高剂量染铝组大鼠脑皮质和海马内presenilin 1、nicastrin均升高(P<0.05)。结论γ-分泌酶水平的升高是铝引起大鼠脑内Aβ蓄积的重要原因之一。Objective To investigate the role of γ-secretase during the accumulation of β amyloid protein（Aβ） induced by aluminum in rat＇s brain.Methods A total of 32 male Sprague-Dawley（SD） rats were randomly divided into control group,low,medium,and high dose group（0.4 mg/kg BW,0.8 mg/kg BW and 1.2 mg/kg BW）.Aluminum-maltolate exposure was conducted by intraperitoneal injection.Eight weeks later,Aβ and γ-secretase（presenilin and nicastrin） were detected with enzym-linked immunosorbent assay（ELISA） and western blot.Results Compared with the control group,the level of Aβ（120.58±23.65 pg/ml）significantly increased in the cortex of high dose group（P〈0.05）,and significantly increased in hippocampus of medium（115.57±7.00 pg/ml）and high dose group （127.09±11.04pg/ml）（P〈0.05）.There was no significant difference in the level of Aβ 40 in cortex and hippocampus of aluminum treated groups compared with that of the control group（P〉0.05）.The level of Aβ 42（51.02±20.90 pg/ml）significantly increased in cotex of high dose group,and in hippocampus of all the aluminum treated groups（24.84±5.05,42.52±12.13,54.42±7.98 pg/ml）.The expression of presenilin 1 and nicastrin increased significantly in cortex and hippocampus of medium and high dose group（P〈0.05）.Conclusion The decreasing of of γ- secretase may be one of the reasons for aluminum-induced accumulation of Aβ.

关 键 词：铝 β-淀粉样蛋白(A13) Γ-分泌酶 早老素1(prosenilin 1) nicastrin蛋白 

分 类 号：R995[医药卫生—毒理学]