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辛伐他汀抑制RhoA蛋白表达、Rho GTPase活性表达逆转兔心室重构

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第3期
页码:
327-331
栏目:
基础研究
出版日期:
2010-04-06

文章信息/Info

Title:
Simvastatin inhibits RhoA translocation and Rho GTPase activity and prevents cardiac hypertrophy in chronic heart failure rabbit models
作者:
齐洪涛1; 2; 刘志华2; 蒋彬1; 邹操1; 赵彩明1; 李红霞1; 宋建平1
1.苏州大学附属第一医院心内科，江苏 苏州 215006；2.青岛大学第二附属医院心功能科 ，山东 青岛 266042
Author(s):
QI Hong-tao;  LIU Zhi-hua;  JIANG Bin;  ZOU Cao;  ZHAO Cai-ming;  LI Hong-xia;  SONG Jian-ping
Department of Cardiology, First Affiliated Hospital, Suzhou University, Suzhou 215006, Jiangsu, China
关键词:
辛伐他汀; 心肌肥厚; RhoA; Rho GTPases; 心力衰竭
Keywords:
simvastatin;  chronic heart failure;  RhoA;  Rho GTPase;  hypertrophy
分类号:
R541.6
DOI:
-
文献标识码:
A
摘要:
目的: 在兔前后负荷增加心力衰竭模型，观察辛伐他订对心肌肥厚、心功能的影响，探讨辛伐他订抑制心肌肥厚、改善心功能的机制。方法: 24只新西兰白兔分为4组，一组假手术组，为健康对照。2、3、4组通过破坏主动脉瓣和缩窄腹主动脉，增加左心室前、后负荷，建立慢性心力衰竭模型；2组：心力衰竭对照组;3组：心力衰竭早干预组,术后每天给与辛伐他汀5 mg/kg灌胃,观察8周;4组：心力衰竭晚干预组：手术4周后每天给与辛伐他汀5 mg/kg灌胃，观察4周。各组术后及观察结束时行超声心动图检查; Western blot分析心肌细白膜RhoA蛋白表达，［γ-32P］ GTP结合分析检测Rho GTPase活性。结果: 早干预组及晚干预组室间隔厚度（IVST）、左心室舒张期内径（LVIDd）、左心室后壁厚度（LVPwd）、左心室收缩期内径（LVIDs）、心脏质量（HW）、左心室质量（LVW）、心脏/体质量比（HW/BW radio）、显著低于心力衰竭对照组，射血分数（EF）、左室长轴缩短率（FS）显著高于心衰对照组。早干预组左心室/体质量比(LVW/BW radio)显著低于心力衰竭对照组。心力衰竭组心肌细胞膜RhoA蛋白表达、Rho GTPase活性明显高于健康对照组，辛伐他汀早干预组及晚干预组心肌细胞膜RhoA蛋白表达及Rho GTPase活性显著低于心力衰竭对照组。 结论: 辛伐他订通过抑制RhoA蛋白由胞浆转至新胞膜、抑制Rho GTPase活性而抑制心肌肥厚,改善心功能。
Abstract:
AIM: To investigate the effects of simvastatin on cardiac hypertrophy and the mechanism in chronic heart failure rabbit models. METHODS: Twenty four New Zealand rabbits were divided into four groups. Group I was designated the normal control group with sham operation. In the other three groups, aortic regurgitation and coarctation of ascending aorta were performed. Group II was designated the heart failure control group, Group III was the early treatment group ［simvastatin 5 mg/(kg·day) postoperatively for 8 weeks］ and Group IV represented the late treatment group ［simvastatin 5 mg/(kg·day) 4 weeks postoperatively for 4 weeks］. On weeks 0 and 8, echocardiographic evaluations were performed. At the eighth postoperative week, heart weight (HW), left ventricular weight (LVW), body weight (BW), heart weight/body weight ratio (HW/BW ratio), and left ventricular weight/body weight radio (LVW/BW ratio) were measured. RhoA expression in cardiomyocyte membrane was analyzed by Western blotting, and Rho GTPases activity was determined by ［γ-32P］ GTP-binding assays. RESULTS: Compared with those in the heart failure control group, IVST, LVIDd, LVPwd, LVIDs, HW, LVW and HW/BW ratio were significantly lower but ejection fraction and fractional shortening were significantly higher in the early and late treatment groups. LVW/BW ratio in the early treatment group was significantly lower than in the heart failure control group. RhoA expression in cardiomyocyte membrane and GTPase activity in the heart failure control group were significantly higher than those in the normal control group but RhoA expression in cardiomyocyte membrane and GTPase activity in early and late treatment groups were significantly lower than in the heart failure control group. CONCLUSION: Simvastatin inhibits the translocation of RhoA from heart cell cytosolic to membrane and thus decreases the activity of Rho GTPase, possibly by reversing left ventricular remodeling and keeping cardiac functions of CHF rabbit model.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2009-06-15.基金项目：江苏省自然科学基金资助项目(BK2005034) 通讯作者：齐洪涛，副主任医师,主要从事慢性心力衰竭机制及临床研究Email:qihongtao06@126.com
更新日期/Last Update: 2010-04-09