厄贝沙坦对急性心肌梗死后晚期心室重构及心室功能的影响
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全军医药卫生科研基金课题资助(01z036)


Effect of Irbesartan on Late Ventricular Remodeling and Ventricular Function After Acute Myocardial Infarction
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    摘要:

    目的观察厄贝沙坦对大鼠心肌梗死后晚期心室重构及心功能的影响。方法结扎大鼠左前降支建立急性心肌梗死模型,将17只术后24 h仍存活的大鼠随机分为对照组(n=8)和厄贝沙坦组(n=9),另设假手术组(n=8)。导管法测量血流动力学参数及心功能;形态学方法测定梗死面积、左心室扩张指数和球形指数;天狼猩红染色偏振光显微镜下测量梗死区及非梗死区Ⅰ型和Ⅲ型胶原容积分数。结果与假手术组比较,对照组大鼠左心室舒张末压、左、右心室相对重量、室间隔厚度、左心室扩张指数、左心室梗死及非梗死区间质Ⅰ型、Ⅲ型胶原容积分数均显著增加(分别为-8.80±4.00比18.94±6.90 mmHg、1.86±0.08比2.30±0.26 mg/g、0.47±0.02比0.57±0.03 mg/g、1.97±0.11比2.63±0.46 mm、0.21±0.04比0.30±0.05、0.26%±0.12%比17.60%±5.26%、0.17%±0.11%比4.22%±3.29%、0.26%±0.12%比3.68%±0.95%、0.17%±0.11%比0.73%±0.26%,均p<0.001);体重、血压、左心室收缩压、球形指数、左心室内压最大上升和下降速率(±dp/dtmax)及其校正值(±dp/dt-max/LVSP)均显著降低(分别为507.9±19.5比392.4±51.8 g、94.82±6.73比70.64±8.77 mmHg、120.38±10.18比85.72±15.12 mmHg、1.79±0.25比1.34±0.104、997±398比2 080±566 mmHg/s-、4 386±728比-1 773±456 mm-Hg/s、41.58±2.57比23.80±4.35、-36.53±6.12比-20.30±3.08,均p<0.001)。与对照组比较,厄贝沙坦组左心室舒张末压、左、右心室相对重量、室间隔厚度、左心室扩张指数、左心室非梗死区Ⅰ型、Ⅲ型胶原容积分数均显著降低(分别为0.62±9.34比18.94±6.90 mmHg、1.93±0.11比2.30±0.26、0.46±0.05比0.57±0.03、1.98±0.22比2.63±0.46 mm、0.23±0.04比0.30±0.05、0.79%±0.39%比3.68%±0.95%、0.37%±0.17%比0.73%±0.26%,p<0.05或p<0.01);左心室球形指数、±dp/dtmax及±dp/dtmax/LVSP显著升高(分别为1.73±0.21比1.34±0.103、490±613比2 080±566 mmHg/s-、2 991±458比-1 773±456 mmHg/s、36.30±2.90比23.80±4.35、-31.20±2.30比-20.30±3.08,均p<0.01)。结论厄贝沙坦能有效地减少左心室非梗死区胶原沉积,抑制大鼠心肌梗死后左心室扩张和球形变,改善左心室重构和左心室功能。

    Abstract:

    Aim To observe effect of irbesartan on late ventricular remodeling and ventricular function after acute myocardial infarction(AMI) in rats. Methods After ligating left anterior descending coronary artery,17 surviving AMI male rats were randomly assigned to AMI control group(n=8) and irbesartan group(n=9).Sham operated group(n=8) was selected randomly as noninfarcted control.After 8 weeks of drug therapy by gastric gavage,hemodynamics and left ventricular function were measured with catheterization;infarcted area,left ventricular dilatation index(ventricular cavity area on mid left ventricular cross-section/ventricular area on mid left ventricular cross-section) and sphericity index were measured and calculated using morphological methods;interstitial type Ⅰ and type Ⅲ collagen volume fraction(CVF) in the infracted and noninfarcted zone(IZ, NIZ) were analyzed using polarized light by picrosirius red staining. Results There was no significant difference in infarcted area between the two AMI groups(40.02% vs 44.70%,p<0.05).Compared with the sham operated group,left ventricular (LV) end diastolic pressure(LVEDP),left and right relative weight(LVRW,RVRW),thickness of interventricular septum,LV dilatation index and the CVF of type Ⅰand type Ⅲ in the IZ and NIZ of LV were all significantly increased in the AMI control group(each result was-8.80±4.00 mmHg vs 18.94±6.90 mmHg,1.86±0.08 mg/g vs 2.30±0.26 mg/g,0.47±0.02 mg/g vs 0.57±0.03 mg/g,1.97±0.11 mm vs 2.63±0.46mm,0.21±0.04 vs 0.30±0.05,0.26%±0.12% vs 17.60% ±5.26%,0.17%±0.11% vs 4.22%±3.29%,(0.26%)±0.12% vs 3.68%±0.95%,0.17%±0.11% vs 0.73%±0.26%,p<0.001),while body weight(BW),blood pressure(BP),left ventricular systolic pressure(LVSP),sphericity index(SI) of LV,the left ventricular pressure maximal rate of rise and fall(±dp/dtmax) and their adjustment by LVSP(±dp/dtmax/LVSP) were significantly decreased(each was 507.9±19.5 g vs 392.4±51.8 g,94.82±6.73 mmHg vs 70.64±8.77 mmHg,120.38±10.18 mmHg vs 85.72±15.12 mmHg,1.79±0.25 vs 1.34±0.10,4 997±398 mmHg/s vs 2 080±566 mmHg/s,-4 386±728 mmHg/s vs -1 773±456 mmHg/s,41.58±2.57 vs 23.8±4.35,-36.53±6.12 vs-20.30±3.08,p<0.001).Compared with the AMI control group,LVEDP,LVRW,RVRW,thickness of interventricular septum,dilatation index of LV and type Ⅰ and Ⅲ CVF in the NIZ of LV were all decreased(each was 0.62±9.34 mmHg vs 18.94±6.90 mmHg,1.93±0.11 vs 2.30±0.26,0.46±0.05 vs 0.57±0.03,1.98±0.22 mm vs 2.63±0.46 mm,0.23±0.04 vs 0.30±0.05,0.79%±0.39% vs 3.68%±0.95%,0.37%±0.17% vs 0.73%±0.26%,p<0.05 or p<0.01),while SI,±dp/dtmax and ±dp/dtmax/LVSP were significantly increased in irbesartan therapy group(each was 1.73±0.21 vs 1.34±0.10,3 490±613 mmHg/s vs 2 080±566 mmHg/s,-2 991±458 mmHg/s vs-1 773±456 mmHg/s,36.30±2.90 vs 23.80±4.35,-31.20±2.30 vs-20.30±3.08,p<0.01). Conclusions Irbesartan can effectively decrease collagen deposition in the NIZ, restrain LV dilatation and spherical change,and then improve left ventricular remodeling and LV function in rats.

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边素艳,刘宏斌,杨庭树.厄贝沙坦对急性心肌梗死后晚期心室重构及心室功能的影响[J].中国动脉硬化杂志,2006,14(8):649~652.

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  • 收稿日期:2005-12-19
  • 最后修改日期:2006-06-20
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