替米沙坦对肾性高血压大鼠心肌重构的影响  

Effect of Telmisartan on Myocardial Remodeling in Rats with Renovascular Hypertention

作　　者：李鑫[1] 冯园园[2] 孙璇璇 李冰[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院药剂科,武汉430022 [2]华中科技大学同济医学院附属协和医院神经内科,武汉430022

出　　处：《医药导报》2015年第9期1161-1164,共4页Herald of Medicine

摘　　要：目的探讨替米沙坦对肾性高血压大鼠心肌重构的影响。方法通过左肾动脉缩窄法建立大鼠肾性高血压心肌肥厚模型,45只雄性斯泼累格·多雷(SD)大鼠随机分为假手术组、模型对照组和替米沙坦组,每组15只。替米沙坦组灌胃替米沙坦10 mg·kg-1·d-1,假手术组、模型对照组灌胃等量纯化水。灌胃8周后,心脏超声诊断仪观察心脏结构和功能,测定血压,计算左心室质量指数,并检测血清中钙调神经磷酸酶(Ca N)含量以及心肌β-肌球蛋白重链(β-MHC)mRNA的表达。结果模型对照组和替米沙坦组左心室射血分数分别为(69.23±1.09)%和(73.77±3.00)%(P<0.05);缩短分数分别为(30.21±2.02)%和(35.29±0.90)%(P<0.05);左心室质量指数分别为(2.83±0.14)和(2.32±0.11)mg·g-1(P<0.05)。与模型对照组比较,替米沙坦组外周循环血液中Ca N以及心肌组织中β-MHC mRNA的表达均下降(均P<0.05)。结论替米沙坦可有效逆转由肾性高血压引起的心肌肥厚,并可能通过抑制起始信号Ca N的活化,作用于下游信号通路,下调心肌蛋白相关基因β-MHC的表达。Objective To investigate the the molecular mechanism of telmisartan for myocardial remodeling in rats with renovascular hypertention. Methods The renovascular hypertensive myocardial hypertrophy model of rats were established by narrowing the left renal artery.The total of 45 mature male SD rats were divided into sham-operated group( n = 15),model control( n = 15) and telmisartan group( n = 15) randomly. The rats in telmisartan group were treated with telmisartan( 10 mg·kg-1·d-1) while those in the sham-operated and model control were reated with the same amounts of distilled water by intragastrical administration. At 8th week of administration,the myocardial structure and function were detected by ultrasonography.The blood pressure was measured by arterial catheterization and calculating the left ventricular mass index( LVMI).The level of serum calcium and nerve phosphatase( Ca N) and the expression of β-myosin heavy chain( β-MHC)mRNA were detected. Results The thickness of left ventricular,ejection fraction [( 69. 23 ± 1. 09) % vs( 73. 77 ± 3. 00) %],fractional shortening[( 30.21±2.02) % vs( 35. 29 ± 0. 90) %],LVMI [( 2. 83 ± 0. 14) mg · g-1vs( 2. 32 ± 0. 11) mg · g-1] were decreased,and the differences were statistically significant( P<0.05).The level of serum calcium and nerve phosphatase( Ca N)and the expression of β-myosin heavy chain( β-MHC) mRNA were decreased in telmisartan treated rats,and the differences were statistically significant( P < 0. 05) when compared with the model control group. Conclusion Telmisartan can improve the myocardial hypertrophy of renovascular hypertensive rats,and it may downregulate the expression of β-MHC by inactivating of the start signal Ca N and its downstream signal pathway.

关 键 词：替米沙坦 高血压 肾性 心肌重构 钙调神经磷酸酶 Β-肌球蛋白重链 

分 类 号：R972.4[医药卫生—药品] R965[医药卫生—药学]