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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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第6期
页码:
846-851
栏目:
基础研究
出版日期:
2010-08-23

文章信息/Info

Title:
Effects of simvastatin on rapamycin-treated cardiac microvascular endothelial cells
作者:
谢晓波; 王东娟; 王晨; 潘庆; 刘楠; 李兰荪; 王海昌
第四军医大学西京医院心血管内科，陕西 西安 710032
Author(s):
XIE Xiao-bo;  WANG Dong-juan;  WANG Chen;  PAN Qing;  LIU Nan;  LI Lan-sun;  WANG Hai-chang
Department of Cardiovascular Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
辛伐他汀; 雷帕霉素; 心肌微血管内皮细胞
Keywords:
simvastatin;  rapamycin;  cardiac microvascular endothelial cell
分类号:
R972;R979.14
DOI:
-
文献标识码:
A
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10 μg/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1 μg/L）。对已加入RAPA（1 μg/L）的细胞中加入不同浓度（0、0.01、0.1、1及10 μmol/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。
Abstract:
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 10 μg/L, respectively, for 24 h. MTT and transwell were used to detect cell viability and migration. The concentration (1 μg/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.

参考文献/References

［1］Steffel J, Tanner FC. Biological effects of drug-eluting stents in the coronary circulation［J］. Herz, 2007, 32(4):268-273.

［2］Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization［J］. Circulation, 2007, 115(18):2435-2441.

［3］Jacobson JR. Statins in endothelial signaling and activation［J］. Antioxid Redox Signal, 2009, 11(4):811-821.

［4］尹志勇,魏丽萍,郝媛媛,等. LY333531对高糖所致心肌微血管内皮细胞通透性上调的拮抗作用［J］. 细胞与分子免疫学杂志, 2009, 25(4): 303-305.

［5］Miriuka SG, Rao V, Peterson M, et al. mTOR inhibition induces endothelial progenitor cell death［J］. Am J Transplant, 2006, 6(9):2069-2079.

［6］Asnaghi L, Bruno P, Priulla M, et al. mTOR: a protein kinase switching between life and death［J］. Pharmacol Res, 2004, 50(6):545-549.

［7］Butzal M, Loges S, Schweizer M, et al. Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro［J］. Exp Cell Res, 2004, 300(1):65-71.

[8] Katsumoto M, Shingu T, Kuwashima R, et al. Biphasic effect of HMG-CoA reductase inhibitor, pitavastatin, on vascular endothelial cells and angiogenesis［J］. Circ J, 2005, 69(12):1547-1555.

[9]Urbich C, Dernbach E, Zeiher AM, et al. Double-edged role of statins in angiogenesis signaling［J］. Circ Res, 2002, 90(6):737-744.

[10]Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis［J］. Circulation, 2002, 105(6):739-745.

[11] Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway［J］. J Clin Invest, 2001, 108(3):391-397.

备注/Memo

备注/Memo:
收稿日期：2009-10-22.通讯作者：王海昌，主任医师，主要从事冠心病基础研究Email：wanghc@fmmu.edu.cn 作者简介：谢晓波，硕士生Email: xixibo@fmmu.edu.cn
更新日期/Last Update: 2010-08-22