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辛伐他汀对心肌梗死后心力衰竭大鼠心肌氧化负荷和心室重构的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第3期
页码:
284-286，290
栏目:
基础研究
出版日期:
2008-05-20

文章信息/Info

Title:
Effects of Simvastatin on oxidative stress of myocardium and ventricular remodeling in postinfarction heart failure rats
作者:
张荷1; 沈潞华1; 庄海舟2; 孙涛3
首都医科大学: 1.附属北京友谊医院心血管中心,2.附属北京友谊医院重症监护病房，北京 100050，
Author(s):
ZHANG He1;  SHEN Luhua1;  ZHUANG Haizhou2;  SUN Tao3
1.Cardiovascular Center, Beijing Friendship Hospital, 2.Intensive Care Unit, Beijing Friendship Hospital, Beijing 100050, China, 3.Cardiovascular center, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China
关键词:
心力衰竭; 辛伐他汀; 大鼠; 氧化负荷
Keywords:
Heart failure;  Simvastatin;  Rats;  oxidative stress
分类号:
R542.22
DOI:
-
文献标识码:
A
摘要:
目的 了解辛伐他汀对急性心肌梗死（AMI）后心衰大鼠心室重构和心功能的影响，并研究NADPH 氧化酶亚基p47phox的变化以研究辛伐他汀在CHF中可能的作用机制。方法 随机选取雄性Sprague Dawly,通过结扎大鼠左冠状动脉前降支制作大鼠AMI模型致CHF,并随机选取大鼠做假手术对照。AMI术后大鼠被随机分为大剂量辛伐他汀组［hSIM, 4 mg/(kg·d)］, 小剂量辛伐他汀组［lSIM, 0.4 mg/(kg·d)］与单纯模型组。干预12周后测体质量（BM）,左室质量(LVM)等,并行血流动力学测定。选取左室非梗死区心肌检测 p47phox mRNA相对表达率及蛋白含量。结果 单纯模型组、hSIM和lSIM组LVM均较假手术组增加;hSIM和 lSIM组平均最大左室压力变化(m±dp/dtmax)均较单纯模型组升高,p47phox mRNA表达、p47phox含量均降低；p47phox含量hSIM和lSIM组组有显著性差异。结论 在AMI后CHF大鼠,大体检查和血流动力学检测可证实辛伐他汀减轻CHF的发展。其机制与NADPH氧化酶亚单位p47phox介导产生的反应性氧簇有关。
Abstract:
AIM To investigate the effects of Simvastatin on ventricular remodeling and cardiac function in postinfarction heart failure rats, to study the changes of p47phox（subunit of NADPH oxidase）and to discuss the possible mechanism of Simvastatin in the treatment of heart failure. METHODS Male Sprague Dawly rats were randomized to CHF group treated with high dose Simvastatin ［hSIM, 4 mg/(kg·d)］ or low dose Simvastatin ［lSIM, 0.4 mg/(kg·d)］, CHF controlled group and shamoperated group. CHF was induced by ligation of the left anterior descending artery to get MI. BM and LVM were weighted and LVM/BM (left ventricular weight to body weight ratio) was calculated. Expression of p47phox mRNA, and p47phoxcontent of the myocardium were studied. RESULTS LVM(g) of lSIM group and hSIM group decreased significantly compared with that of the vehicles. The m dp/dt max of SIM groups rose significantly compared with that of the vehicles. The p47phox mRNA expression and p47phox content decreased in SIM group or hSIM group compared with those of the vehicles. There was significant difference of the p47phoxcontent between the lSIM group and hSIM group. CONCLUSION In post AMI (acute myocardial infarction) CHF rats, the intervention of Simvastatin ameliorates ventricular remodeling and modifies the evolvement of heart failure by ROS (reactive oxidative species) mediated by NADPH oxidase subunit p47phoxin postinfarction heart failure rats.

参考文献/References

［1］ Folkeringa RJ, Van Kraaij DJ, et al. Statins associated with reduced mortality in patients admitted for congestive heart failure ［J］. J Card Fail, 2006, 12(2):134-138.

［2］ Maack C, Kartes T, Kilter H, et al. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1GTPase and represents a target for statin treatment［J］. Circulation, 2003, 108(13):1567-1574.

［3］ 杜荣增，任雨笙，廖德宁,等.充血性心力衰竭患者口服ACEIs后血浆oxLDL、vWF及TAC改变的临床意义［J］. 心脏杂志, 2006, 18（4）:422-424.

［4］ Maack C, Kartes T, Kilter H. et al. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1GTPase and represents a target for statin treatment ［J］. Circulation, 2003, 108(13):1567-1574.

［5］ 刘宇宏，曾秋棠，毛晓波,等. 氟伐他汀防治缺血性心脏病心衰及其抗氧化应激作用的实验研究［J］. 心脏杂志, 2005, 17（1）：21-24，28.

备注/Memo

备注/Memo:
收稿日期：2007-01-06.通讯作者:沈潞华，主任医师，主要从事心力衰竭研究Email:shenluhua666@sina.com.cn 作者简介:张荷，主治医师，博士生Email:sence2007@yahoo.com.cn
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