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辛伐他汀早期干预能更有效抑制压力负荷高血压大鼠心肌肥厚

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第2期
页码:
151-155,160
栏目:
基础研究
出版日期:
2010-12-10

文章信息/Info

Title:
Early intervention with simvastatin exerts improved effects on cardiac hypertrophy in pressure-overload rats than late intervention
作者:
尚福军1; 王捷频2; 郑强荪1; 刘雄涛1; 薛玉生1; 李军1; 赵连友1
1.第四军医大学：1.唐都医院心脏内科，2.药学系药物研究所，陕西 西安 710032
Author(s):
SHANG Fu-jun1;  WANG Jie-pin2;  ZHENG Qiang-sun1;  LIU Xiong-tao1;  XUE Yu-sheng1;  LI Jun1;  ZHAO Lian-you1
1.Department of Cardiology, Tangdu Hospital, Xi’an 710038, Shaanxi, China, 2.Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
辛伐他汀; 高血压; 心肌肥厚; 药物干预
Keywords:
simvastatin;  hypertension;  cardiac hypertrophy;  medical intervention
分类号:
R54
DOI:
-
文献标识码:
A
摘要:
目的: 比较辛伐他汀早期干预与晚期干预对高血压心肌肥厚的防治效果，并初步探讨其机制。方法： 采用腹主动脉缩窄法建立压力负荷高血压大鼠模型，在心肌肥厚形成的不同阶段分别给予辛伐他汀［10 mg/(kg·d)，ig］干预。采用天狼猩红染色、血流动力学测定等方法，观察和比较辛伐他汀对高血压心肌肥厚和心功能的影响。应用ELISA法检测心肌组织中TNF-α、IL-6和IL-10蛋白的含量。根据Fenton反应原理应用细胞色素C还原实验测定心肌内活性氧（ROS）的水平和还原型辅酶II （NADPH）氧化酶的活性。结果： 与假手术组比较，腹主动脉缩窄后8周，大鼠左室质量指数、心肌组织中胶原的含量明显升高，左室舒张功能明显下降（P<0.01）。在不同阶段给予辛伐他汀干预，均可降低左室质量和心肌中胶原的含量；与晚期干预组比较，早期辛伐他汀干预组大鼠左室质量和心肌中胶原的含量更低（P<0.05），并可提高左室舒张功能。压力负荷大鼠心肌组织内TNF-α和IL-6的水平显著升高（P<0.01），ROS的水平和氧化酶的活性亦明显升高（P<0.01）；辛伐他汀干预可明显降低TNF-α、IL-6和ROS的水平以及氧化酶的活性，但与晚期干预组比较，早期辛伐他汀干预组大鼠心肌组织内TNF-α、IL-6和ROS的水平以及氧化酶的活性更低（P<0.05）。结论： 在高血压的早期给予辛伐他汀干预，对高血压心肌肥厚的改善作用优于晚期药物干预，因辛伐他汀早期干预能更有效地抑制心肌组织炎性因子的表达和ROS生成。
Abstract:
AIM: To compare the effects of early and late intervention with simvastatin on cardiac hypertrophy and to investigate the probable molecular mechanisms. METHODS: In pressure-overload rat model induced by abdominal aortic coarctation, simvastatin ［10 mg/(kg·day), IG］ was administrated at early or late stage and structural and functional changes were observed by histopathology analysis with picrosirius staining and hemodynamic measurement. The expression of TNF-α and IL-6 and IL-10 protein levels were determined by ELISA and the production of reactive oxygen species (ROS). Activity of NAPDH oxidase in myocardium were measured, respectively, by Fenton reaction and by superoxide dismutase inhibitable cytochrome C reduction assay. RESULTS: In rats at 8 weeks after aortic coarctation, the left ventricle weight and collagen volume fraction in myocardium significantly increased and cardiac diastolic function decreased, compared with those in sham-operated rats (P<0.01). Intervention with simvastatin at early and late stages both markedly decreased the left ventricle weight and collagen volume fraction (P<0.05). However, left ventricle weight and collagen volume fraction in early intervention group were lower than those in late intervention group (P<0.05). The early intervention also improved the diastolic function and the contents of TNF-α and IL-6. ROS production and NADPH oxidase activity in myocardium were all elevated in pressure-overload rats, which were attenuated by simvastatin intervention at both stages. Contents of TNF-α and IL-6, production of ROS, and activity of NADPH oxidase in rats in early intervention group were lower than those in late intervention group (P<0.05). CONCLUSION: The effects of early intervention with simvastatin on cardiac hypertrophy in pressure-overload rats are superior to those of late intervention, which is probably attributed to the stronger inhibitory effects of early intervention with simvastatin on the expression of proinflammatory cytokines and production of ROS.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2010-05-11.基金项目：国家十一五科技支撑计划高血压综合防治研究子课题项目资助（2006BAI01A03） 通讯作者：赵连友，主任医师，主要从事高血压发病的分子生物学机制及防治研究 Email：zhaolyfmmu@yahoo.com.cn 作者简介：尚福军，讲师，博士Email：wangjp@163.com
更新日期/Last Update: 2010-12-10