阿托伐他汀对兔缺血再灌注损伤的保护作用

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (7): 786-789.

阿托伐他汀对兔缺血再灌注损伤的保护作用

周逸, 陈曼华, 刘锦华, 张利芸

武汉市中心医院心血管内科, 武汉 430014, 湖北

收稿日期:2007-02-26 修回日期:2007-06-13 出版日期:2007-07-26 发布日期:2020-10-27
通讯作者: 陈曼华, 女, 主任医师, 教授, 研究方向:冠心病的介入治疗及基础研究。Tel:027-82811080-8210 E-mail:sjcmh@yahoo.com.cn
作者简介:周逸,男,硕士,主治医师,研究方向:心血管药理。Tel:027-82811080-8209 E-mail:zy1295090909@yahoo.com.cn

Protection of atorvastatin on cardiac function following ischemia-reperfusion injury in rabbits

ZHOU Yi, CHEN Man-hua, LIU Jin-hua, ZHANG Li-yun

Department of Cardiology, Wuhan Central Hospital, Wuhan 430014, Hubei, China

Received:2007-02-26 Revised:2007-06-13 Online:2007-07-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 观察阿托伐他汀(ATV) 对心肌缺血再灌注损伤的影响以及诱导型一氧化氮合酶(iNOS) 在其中的作用。方法: 将健康雄性新西兰大耳白兔随机分成模型对照组、ATV 组、ATV+S-甲基异琉脲硫酸盐(SMT) 组、SMT 组, 每组8 只。进行40 min 局部缺血和240 min 再灌注, 观察各组血流动力学、血液生物化学及一氧化氮合酶的变化。结果: 缺血再灌注使左室发展压(LVDP) 和压力上升最大速率(+dp/dt_max) 分别下降24.6%和35.3%;3 d ATV 预处理(10 mg·kg^-1·d^-1) 使缺血再灌注后LVDP 和+dp/dt_max的下降幅度分别减小21.7%和41.3%, 使心肌型肌酸激酶同功酶(CK-MB) 和乳酸脱氢酶(LDH-1)分别降低31.4%和19.1%, 使iNOS 上升102.6%;ATV+SMT 组LVDP 和+dp/dt_max 的下降幅度、CKMB、LDH-1、iNOS 均和模型对照组无明显差异。结论: ATV 预处理通过上调iNOS 减轻心肌缺血再灌注损伤。

关键词: 阿托伐他汀, 兔, 心肌, 缺血再灌注, 一氧化氮合酶

Abstract: AIM: To observe the effect of atorvastatin (ATV) on myocardial ischemia-reperfusion injury and the role of inducible nitric oxide synthase (iNOS). METHODS: The rabbits were randomly divided into control group, ATV group, ATV+S-Methylisothiourea sulfate (SMT) group, SMT group.All rabbits were subjected to 40 min ischemia and 240 min reperfusion.The hemodynamic variables, CK-MB, LDH-1 and nitric oxide synthase were detected after reperfusion. RESULTS: LVDP and+dp/dt_max decreased by 24.6% and 35.3%respectively following ischemia-reperfusion.Pre-treated by ATV (10 mg·kg^-1·d^-1) for three days, LVDP and+dp/dt_max decreased by 21.7% and 41.3%, CK-MB and LDH-1 by 31.4% and 19.1% and iNOS increased to 102.6%.The reduction of LVDP and+dp/dt_max, CKMB, LDH-1 and iNOS in ATV+SMT group was no statistically significant with those in control group. CONCLUSION: ATV pretreatment protected myocardial ischemia-reperfusion injury by upregulating iNOS.

Key words: atorvastatin, rabbit, myocardium, ischemia-reperfusion, nitric oxide synthase

中图分类号:

R965.2

周逸, 陈曼华, 刘锦华, 张利芸. 阿托伐他汀对兔缺血再灌注损伤的保护作用[J]. 中国临床药理学与治疗学, 2007, 12(7): 786-789.

ZHOU Yi, CHEN Man-hua, LIU Jin-hua, ZHANG Li-yun. Protection of atorvastatin on cardiac function following ischemia-reperfusion injury in rabbits[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(7): 786-789.

参考文献

1 Spencer FA, Allegrone J, Goldberg RJ, et al.Association of statin therapy with outcomes of acute coronary syndromes:the GRACE study[J].Ann InternMed, 2004;140:857-866.
2 Ray KK, Cannon CP.The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes[J].J Am Coll Cardiol, 2005;46:1425-1433.
3 Ito MK, Talbert RL, Tsimikas S.Statin-associated pleiotropy: possible beneficial effects beyond cholesterol reduction [J]. Pharmacotherapy, 2006;26:S85-S97.
4 Ikeda Y, Young LH, Lefer AM.Rosuvastatin, a new HMGCoA reductase inhibitor, protects ischemic reperfused myocardium in normocholesterolemic rats[J].J Cardiovasc Pharmacol, 2003;41:649-656.
5 秦晋梅, 杨波, 李建军, 等.氟伐他汀对高脂血症兔心肌缺血再灌注损伤心肌局部细胞间粘附分子-1 的影响[J].中国临床药理学与治疗学, 2004;9:87-90.
6 Tiefenbacher CP, Kapitza J, Dietz V, et al.Reduction of myocardial infarct size by fluvastatin[J].Am J Physiol Heart Circ Physiol, 2003;285:H59-H64.
7 Tavackoli S, Ashitkov T, Hu ZY, et al.Simvastatin-induced myocardial protection against ischemia-reperfusion injury is mediated by activation of ATP-sensitive K⁺ channels[J].Coron Artery Dis, 2004;15:53-58.
8 Cohen MV, Yang XM, Downey JM.Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies[J].Cardiovasc Res, 2006; 70:231-239.
9 Di Napoli P, Antonio Taccardi A, Grilli A, et al.Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression:an ex vivo study in isolated working rat hearts[J]. Cardiovasc Res, 2001;51:283-293.
10 Di Napoli P, Taccardi AA, Grilli A, et al.Chronic treatment with rosuvastatin modulates nitric oxide synthase expression and reduces ischemia-reperfusion injury in rat hearts[J].Cardiovasc Res, 2005;66:462-471.
11 Jones SP, GibsonMF, Rimmer DM 3rd, et al.Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor[J].J Am Coll Cardiol, 2002;40:1172-1178.
12 Guo Y, Jones WK, Xuan YT, et al.The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene [J].Proc Natl Acad Sci USA, 1999;96:11507-11512.
13 Wang Y, Guo Y, Zhang SX, et al.Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocytes [J].JMol Cell Cardiol, 2002;34:5-15.
14 Zhao T, Xi L, Chelliah J, et al.Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors:evidence from gene-knockout mice[J].Circulation, 2000;102:902-907.
15 Hattori Y, Nakanishi N, Kasai K.Statin enhances cytokinemediated induction of nitric oxide synthesis in vascular smooth muscle cells[J].Cardiovasc Res, 2002;54:649-658.
16 Kato T, Hashikabe H, Iwata C, et al.Statin blocks Rho Rhokinase signalling and disrupts the actin cytoskeleton:relationship to enhancement of LPS-mediated nitric oxide synthesis in vascular smooth muscle cells[J].Biochim Biophys Acta, 2004; 1689:267-272.

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