辛伐他汀通过抗异戊二烯化途径对转β分泌酶HEK293细胞分泌β淀粉样蛋白的影响  

Effect of simvastatin on Aβ secretase HEK293-secreted β amynoid via anti-isoprenoid pathway

作　　者：刘郡[1] 朱天瑞[2] 李晓红[2] 

机构地区：[1]山东大学医学院,济南250031 [2]山东大学附属医院济南市中心医院神经内科

出　　处：《中华老年心脑血管病杂志》2013年第6期645-647,共3页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：山东省自然科学基金(Y2008C103);济南市科技发展计划项目(200807032)

摘　　要：目的探讨辛伐他汀通过抑制类异戊二烯小分子生成途径对转β分泌酶基因的细胞分泌β淀粉样蛋白(Aβ)的影响,并探讨相关机制。方法细胞到对数生长期后,可分为辛伐他汀组和对照组,辛伐他汀组分别加入1、5、10μmol/L辛伐他汀,MTT测定细胞活性;COD-PAP法检测24、48h细胞内胆固醇含量;ELISA法检测细胞上清Aβ1-40,Aβ1-42;Western blot检测细胞上清可溶性淀粉样前体蛋白α。结果辛伐他汀组1、5μmol/L Aβ1-40和Aβ1-42分泌量较对照组明显下降(P<0.05),加入250μmol/L甲羟戊酸后,可逆转Aβ1-40和Aβ1-42分泌量(P<0.05,P<0.01);辛伐他汀组1、5μmol/L细胞外液可溶性淀粉样前体蛋白α的分泌量较对照组明显升高,加入250μmol/L甲羟戊酸能逆转这种趋势(P<0.01)。结论辛伐他汀通过抗异戊二烯小分子的生成能降低细胞外液Aβ分泌量,可能与增强α分泌酶途径,从而显著的增加可溶性淀粉样前体蛋白α的分泌量有关。Objective To study the effect of simvastatin on Aβ secretase HEK293-secreted β amy- noid via the anti-isoprenoid pathway and its mechanism. Methods Cells at the logarithmic multi- plcatin phase were divided into control group and 1μmol/L simvastatin group,5μmol/L simvas- tatin group and 10 μmol/L simvastatin group. Viability of the cells was assayed by MTT. Intracel- lular cholesterol level was measured at 24 and 48 h, respectively,with the COD-PAP method. Ex- pressions of secreted Aβ1-40, Aβ1-42 and soluble amyloid precursor protein a were detected by ELISA and Western blot, respectively. Results No significant difference was found in the cell morphology and intracellular cholesterol level between 1 μmol/L and 5 μmol/L simvastatin groups at 24 and 48 h （P〉0.05）. The Aβ1-40 and Aβ1-42 secretion volume was significantly lower in 5 μmol/L simvastatin group than in 1 μmol/L simvastatin group （P〈0. 05）. Mevolanate （250μmol/L） could reverse the Aβ1-40 and Aβ1-42 secretion volume （P〈0.05,P〈0.01）. The soluble amyloid precursor protein a secretion volume was significantly higher in 1 μmol/L and 5 μmol/L simvastatin groups than in control group （P〈0.01） and mevolanate （250 μmol/L） could reverse such a tendency. Conclusion Simvastatin can reduce the Aβ secretion through the production of anti-isoprenoid small molcules, which may be related with the a secretase and the soluble amyloid precursor protein a secretion.

关 键 词：斯伐他汀 淀粉样Β蛋白 细胞外液 异戊烯化 

分 类 号：R965[医药卫生—药理学]