辛伐他汀对雷帕霉素作用下的大鼠心肌微血管内皮细胞的影响  

Effects of simvastatin on rapamycin-treated cardiac microvascular endothelial cells

作　　者：谢晓波[1] 王东娟[1] 王晨[1] 潘庆[1] 刘楠[1] 李兰荪[1] 王海昌[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032

出　　处：《心脏杂志》2010年第6期846-851,共6页Chinese Heart Journal

摘　　要：目的:探讨辛伐他汀(SIM)对雷帕霉素(RAPA)作用下大鼠心肌微血管内皮细胞(CMECs)增殖、迁移、凋亡及一氧化氮(NO)分泌的影响。方法:用不同浓度(0、0.01、0.1、1及10μg/L)的RAPA处理CMECs 24 h,分别采用MTT比色法及transwell法检测细胞的增殖能力和迁移能力,并选择合适干扰浓度(抑制效果居中,即对细胞的增殖及迁移有一定的抑制作用,但不会完全抑制,选择浓度为1μg/L)。对已加入RAPA(1μg/L)的细胞中加入不同浓度(0、0.01、0.1、1及10μmol/L)的SIM,共孵育24 h,采用MTT比色法检测细胞的增殖能力,用transwell法检测细胞迁移能力,用Hoechst染色法计算细胞的凋亡率,用Griess反应检测NO的分泌活性。结果:与对照组相比较,单纯以RAPA干预细胞后,细胞增殖和迁移的能力均显著下降(P<0.05,P<0.01),且呈浓度依赖性。而在RAPA基础上加入不同浓度的SIM后,与单纯RAPA组比较,细胞的增殖能力及迁移能力均显著增强(P<0.05,P<0.01),NO的分泌活性明显升高(P<0.05),细胞的凋亡率明显下降(P<0.05)。结论:RAPA能抑制CMECs增殖及迁移、NO分泌并诱导其凋亡。而将CMECs与SIM共孵育24 h后,对RAPA诱导的细胞损伤具有抑制作用。AIM： To investigate the effects of simvastatin （SIM） on the proliferation, migration, apoptosis and nitric oxide secretion of rapamycin （RAPA）-treated cardiac microvascular endothelial cells （CMECs）. METHODS： CMECs were isolated from rat left ventricle and cultured. They were then added with RAPA at the concentration of 0, 0. 01,0. 1, 1 and 10μg//L, respectively, for 24 h. MTF and transwell were used to detect cell viability and migration. The concentration （1μg//L） was then chosen for the next experiment. CMECs with RAPA （1 μg/L） were added with SIM at the concentrations of 0. 01, 0. 1, 1 and 10 mol/L, respectively, and cultured for 24 h and proliferation and migration were detected by MTT and transwell. The secretion of NO was assessed by Griess reaction and morphological assessment of apoptosis was performed by Hoechst 33258 staining. RESULTS： RAPA significantly inhibited proliferation and migration of CMECs （P 〈 0.05, P 〈 0.01 vs. control group） in a concentration-dependent manner. However, compared with those in single RAPA-treated group, the proliferation and migration of the groups treated with different concentrations of SIM ＋ RAPA （1 μg/L） increased （P 〈0. 05, P 〈0. 01 ）, the secretion of NO increased （ P 〈 0.05 ） and the rates of apoptosis decreased （ P 〈 0. 05 ）. CONCLUSION ： RAPA inhibits proliferation, migration and NO secretion and induces apoptosis of CMECs. SIM may protect CMECs from these impaired effects via RAPA.

关 键 词：辛伐他汀 雷帕霉素 心肌微血管内皮细胞 

分 类 号：R972[医药卫生—药品] R979.14[医药卫生—药学]