我们的网站为什么显示成这样?

可能因为您的浏览器不支持样式,您可以更新您的浏览器到最新版本,以获取对此功能的支持,访问下面的网站,获取关于浏览器的信息:

|本期目录/Table of Contents|

阿托伐他汀对自发性高血压大鼠心肌组织p21表达的影响及其意义

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第2期
页码:
134-138141
栏目:
基础研究
出版日期:
2014-10-25

文章信息/Info

Title:
Effects of atorvastatin on p21 expression in hypertrophic myocardium of spontaneously hypertensive rats
作者:
赵丽丽蒲丽君赵 珂罗 勇
(川北医学院附属医院心内科,四川 南充 637000)
Author(s):
ZHAO Li-li PU Li-jun ZHAO Ke LUO Yong
(Department of Cardiology, Affiliated Hospital, North Sichuan Medical College, Nanchong 637000, Sichuan, China)
关键词:
阿托伐他汀自发性高血压大鼠心肌肥厚p21大鼠
Keywords:
atorvastatin spontaneously hypertensive rats left ventricular hypertrophy P21 rat
分类号:
R541 .3
DOI:
-
文献标识码:
A
摘要:
目的:观察阿托伐他汀(ATV)对自发性高血压大鼠(SHR)心肌组织中p21表达的影响,探讨其改善心肌肥厚的可能机制。方法:将16只8周龄SHR随机分为2组(n=8):ATV药物干预组(ATV组)与SHR模型对照组(SHR组),并以8只同周龄Wistar-Kyoto大鼠作为正常对照组(WKY组)。ATV组用ATV 50 mg/(kg·d)灌胃,SHR组与WKY组采用等容量蒸馏水每日同时灌胃。每隔2周测1次血压。10周后, 观察大鼠血脂、心肌肥厚指标、p21 mRNA及其蛋白表达的改变。结果:干预 10周后,ATV组及SHR组血脂、血压无明显差异。ATV组左室质量指数低于SHR组(P<0.01)。ATV组p21mRNA及蛋白的表达明显高于SHR组(P<0.01)。心肌组织p21 mRNA的表达与全心质量与体质量比(HW/BW)呈负相关(r=-0.709,P<0.01),与左室质量与体质量比(LVW/BW)呈负相关(r=-0.665,P<0.01)。结论:ATV可上调SHR肥厚心肌组织中p21的表达,可有效改善左室肥厚。
Abstract:
AIM:To examine the effect of atorvastatin on p21 expression of left ventricular hypertrophy in spontaneously hypertensive rats (SHR) and the underlying mechanisms of atorvastatin in alleviating myocardial hypertrophy. METHODS: Sixteen 8-week-old male SHR were randomly divided into ATV group (n=8) and SHR group (n=8). Age-matched Wistar-Kyoto rats served as normotensive control group (WKY group, n=8). In ATV group, atorvastatin was given at a dose of 50 mg/kg per day by gastric gavage. In the SHR group and WKY group, the same volume of distilled water was given. Blood pressure was measured every 2 weeks and after 10 weeks, plasma lipid levels were measured. Ventricular weight index was calculated by the ratio of left ventricular weight to body weight and p21 expressions were examined by immunohistochemistry analysis and RT-PCR. RESULTS: No significant difference was found in plasma lipid levels and blood pressure between ATV group and SHR group. Compared with that in the SHR group, left ventricular weight index decreased significantly in the ATV group (P<0.01) and the myocardium p21 expression increased significantly (P<0.01). The expression of p21mRNA in cardiomyocytes were negatively correlated with HW/BW (r=-0.709, P<0.01) and LVW/BW (r=-0.665, P<0.01). CONCLUSION: Atorvastatin increases myocardium P21 expression and alleviates left ventricular hypertrophy in spontaneously hypertensive rats.

参考文献/References

[1]Beltrami AP,Urbanek K,Kajstura J,et al.Evidence that human cardiac myocytes divide after myocardial infarction[J].N Engl J Med,2001,344(23):1750-1757.
[2]盛 瑞,顾振纶.超负荷心肌肥厚心肌细胞的凋亡和增殖[J].中国药理学通报,2005,21(5):531-535.
[3]Liu W,Zi M,Naumann R,et al.Pak1 as a novel therapeutic target for antihypertrophic treatment in the heart[J].Circulation,2011,124(24):2702-2715.
[4]Taglieri DM,Monasky MM,Knezevic IA,et al.Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A[J].J Mol Cell Cardiol, 2011, 51(6):988-996.
[5]Pullamsetti SS,Doebele C,Fischer A,et al.Inhibition of MicroRNA-17 improves lung and heart function in experimental pulmonary hypertension[J].Am J Respir Crit Care Med,2012,185(4):409-419.
[6]Li JM,Brooks G. Downregulation of cyclin-dependent kinase inhibitors p21 and p27 in pressure-overload hypertrophy[J].Am J Physiol,1997,273(3):H1358-H1367.
[7]Sparrow CP,Burton CA,Hernandez M,et al.Simvastatin has anti-inflame-matory and antiatherosclerotic activities Independent of plasma cholesterol lowering[J].Arterioscler Thromb Vasc Biol,2001,21(1):115-121.
[8]Paradiso-Hardy FL,Gordon WL,Jackevicius CA,et al.The importance of in-hospital statin therapy for patients with acute coronary syndromes[J].Pharmacotherapy,2003,23(4):506-513.
[9]Keech A,Colquhoun D,Best J,et al.Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose - Results from the LIPID trial[J].Diabetes Care,2003, 26(10):2713-2721.
[10]Assmus B, Urbich C, Aicher A, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes[J].Circ Res,2003,92(9):1049-1055.
[11]Lee SJ,Ha MJ,Lee J,et al.Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme a reductase pathway induces p53-independent transcriptional regulation of p21WAF1/CIP1 in human prostate carcinoma cells[J].J Biol Chem,1998,273(17):10618-10623.
[12]Rao S,Lowe M,Herliczek TW,et al.Lovastatin mediated G1 arrest in normal and tumor breast cell is through inhibition of CDK2 activity and redistribution of p21WAF1 and p27,Independent of p53[J].Oncogene,1998,17(18):2393-2402.
[13]Ge CJ,Lu SZ,Chen YD,et al.Synergistic effect of amlodipine and atorvastatin on blood p ressure, left ventricular remodeling,and C-reactive protein in hypertensive patients with primary hypercholesterolemia[J].Heart Vessels,2008,23(2):91-95.
[14]Ogata Y,Takahashi M,Takeuchi K,et al.Fluvastatin induces apoptosis in rat neonatal cardicmyocytes:a possible mechanism of statin-attenuated cardiac hypertrophy[J].J Cardiovasc Pharmacol,2002,40(6):907-915.
[15]Mondo CK,Yang WS,Su JZ,et al.Atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat[J].Clin Exp Hypertens,2006,28(5):499-509.

备注/Memo

备注/Memo:
收稿日期:2014-05-04.
通讯作者:罗勇,主任医师,主要从事心血管疾病临床与基础研究 Email:luoyong226@126.com
作者简介:赵丽丽,住院医师,硕士生 Email:81740931@ qq.com 共同第一作者:蒲丽君,主治医师,硕士 Email:pushanshan1978@ 163.com
更新日期/Last Update: 2014-11-18