Simvastatin induces eosinophil apoptosis in vitro
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF TUBERCULOSIS AND RESPIRATORY DISEASES
- Issue:
- 5
- DOI:
- 10.3760/j:issn:1001-0939.2005.05.008
- Key Word:
- 辛伐他汀;哮喘;嗜酸粒细胞;细胞凋亡
Abstract： 目的研究降脂药辛伐他汀对支气管哮喘(简称哮喘)外周血嗜酸粒细胞(EOS)凋亡的影响及其机制.方法分离10例患者外周血EOS,加入不同浓度辛伐他汀 (1、5、10、20 μmol/L)和甲羟戊酸(MVA,100 μmol/L)进行体外培养,并以0 μmol/L辛伐他汀作为空白对照组,用流式细胞术检测EOS凋亡,用酶联免疫吸附测定(ELISA)法检测EOS活化半胱氨酸天冬氨酸蛋白酶3(caspase-3)水平.结果 (1)EOS与辛伐他汀(5 μmol/L)共同孵育6、12、24、48 h凋亡率分别为(32±4)%、(47±7)%、(62±9)%、(86±14)%,对照组分别为(23±3)%、(24±3)%、(41±6)%、(70±12)%,两组在同一时点比较差异有统计学意义(P=0.000).(2)EOS体外培养12 h,1 μmol/L辛伐他汀即可促进EOS凋亡, 此作用在5 μmol/L时达最大效应. 1、5、10、20 μmol/L辛伐他汀共培养EOS凋亡率分别为(37±3)%、(51±3)%、(53±4)%、(52±4)%, 与空白对照组[ (24±3)%]比较差异也有统计学意义 (P=0.000).(3)活化caspase-3水平变化与EOS凋亡率一致.EOS体外培养12 h时 1、5、10、20 μmol/L辛伐他汀共培养分别为(14±4) μg/L、(22±4) μg/L、(24±4)μg/L、(23±5) μg/L,与空白对照组[(8±3) μg/L]比较,差异有统计学意义(P=0.000～0.003).(4)辛伐他汀可促进EOS凋亡及增加EOS活化caspase-3水平的作用可被MVA完全阻断,体外培养12 h, EOS凋亡率在空白对照组、20 μmol/L辛伐他汀组、20 μmol/L辛伐他汀+MVA组(100 μmol/L)分别为(24±3)%、(52±4)%、(25±3)% , 活化caspase-3分别为(8±3) μg/L、(23±5) μg/L和(9±3) μg/L.结论辛伐他汀可能通过抑制类异戊二烯通路,干扰Ras蛋白的法呢基化,促进哮喘患者外周血EOS凋亡.
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