阿托伐他汀改善自发性高血压大鼠的心肌脂质代谢和抑制心肌肥厚  

Atorvastatin Improves Cardiac Lipid Metabolism in Spontaneous Hypertensive Rats and Ameliorates Cardiac Hypertrophy

作　　者：孙雅逊[1] 胡申江[1] 张志杰[1] 康兰[1] 赵晓燕[1] 郑霞[1] 

机构地区：[1]浙江大学医学院附属第一医院心内科,浙江杭州310003

出　　处：《中华高血压杂志》2006年第8期632-635,共4页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助项目(30470715);国家教育部博士学科专项科研基金(20040335118)

摘　　要：目的通过研究阿托伐他汀对自发性高血压大鼠(SHR)心肌中PPARα、CPTⅠ表达和心肌脂质代谢变化及心肌肥厚指标的影响,探讨阿托伐他汀对SHR心肌肥厚的改善作用及其机理。方法观察阿托伐他汀灌胃10周的SHR心肌肥厚指标、血清和心肌游离脂肪酸含量及心肌PPARα、CPTⅠmRNA表达的改变。结果与WKY(n=6)比较,SHR(n=6)心肌中PPARαmRNA(0.285±0.062比WKY:0.478±0.093,P<0.01)与CPTⅠmRNA(0.795±0.139比WKY:1.115±0.109,P<0.01)表达减少,血清及心肌中游离脂肪酸含量增加,分别为[(798.2±38.0比WKY:354.7±27.7)nmol/L,P<0.01]和[(635.0±77.4比WKY:245.3±47.3)nmol/L,P<0.01],心室质量指数增加(VWI)[(3.16±0.08比WKY:2.99±0.10)g/kg,P<0.05],心肌细胞直径增加(TDM)[(21.3±1.3比WKY:18.18±0.75)μm,P<0.01];阿托伐他汀50mg/kg·d治疗10周后(n=6),心肌中PPARα、CPTⅠmRNA表达增加,心肌中游离脂肪酸含量明显降低、VWI降低,TDM降低。结论阿托伐他汀能够增加心肌中PPARα、CPTⅠmRNA表达,降低心肌中游离脂肪酸含量,改善心肌脂质代谢障碍,可能是其抑制心肌肥厚发生与发展的机制之一。Objective To investigate the effect of atorvastatin on cardiac lipid metabolism and cardiac hypertrophy. Methods SHR（n=61 and WKY（n=61 were given atorvastatin 50 mg/kg · d body weight by gavage. After 10 weeks, LV/BW ratio, serum free fatty acid（FFA）, peroxisome proliferator-activated receptor α（PPARα） and carnitime palmitoyltransferase（CPT- I ） mRNA in myocardium were investigated. Results Serum and myocardial free fatty acid in SHR were higher than that in WKY（seurm FFA： SHR：798.2±38.0 vs WKY：354.7±27.7 nmol/L, P〈0.01）; （myocardium：635.0±77.4 vs 245.3± 47.3 nmol/L, P〈0.01）. The expression of PPARa and CPT- I mRNA in myocardium in SHR was decreased as compared with those in WKY group（0. 285±0. 062 vs WKY： 0. 478±0. 093, P〈0.01; 0. 795 ±0. 139 vs WKY： 1. 115±0. 109, P〈0.01 respectively）, VWI and TDM in SHR were greater than those in WKY （3. 16±0.08 vs WKY： 2.99±0.10 g/kg, P〈0.05; 21.32±1.25 vs WKY： 18. 18＋0.75 μm, P 〈0.01 ）. Atorvastatin decreased serum fatty acid （571.0±40.8 vs control：798.2±38. 0 nmol/L, P〈 0.01 ） and free fatty acid in cardiac myocytes （ 287. 7 ± 57.7 vs control： 635. 0 ±77.4 nmol/L, P〈0.01 ）. Meanwhile, the expression of PPARα and CPT- I mRNA in myocardium in atorvastatin group were increased （PPARα mRNA： 0. 457±0. 075 vs control：0. 285±0. 062, P〈0. 01; CPT- I mRNA： 1. 037±0. 101 vs control： 0. 795±0. 139, P〈0.05） in associated with lower VWI and TDM（2.98±0. 05 vs contro1：3.16±0.08 g/kg, P〈0.01; 18.91±1.05 vs control： 21. 32 ±1. 25μm, P〈0.05）. Conclusion Atorvastatin may ameliorate cardiac hypertrophy by improves cardiac lipid metabolism in the SHR.

关 键 词：阿托伐他汀 心肌肥厚 过氧化物酶体增殖物激活受体 游离脂肪酸 

分 类 号：R544.1[医药卫生—心血管疾病]