福辛普利、依贝沙坦及二者合用对心肌梗死后心室重塑影响的实验研究

目的：对比福辛普利、依贝沙坦及二合用对大鼠心肌梗死后心室重塑的影响。方法：通过结扎冠状动脉左前降支诱导大鼠心肌梗死，心肌梗死后24h将大鼠随机分为：（1）安慰剂组；（2）福辛普利组；（3）依贝沙坦组；（4）福辛普利＋依贝沙坦组；另设假手术组。2周后检查以下指标：（1）平均动脉压，左室舒张末压；（2）心室重量／体重；（3）非梗死区胶原含量；（4）非梗死区非心肌细胞增生数量。结果：安慰剂组与假手术组相比左室舒张末压增加（P＜0．05），且心室重量／体重、非梗死区胶原含量及非心肌细胞增生数量增加显（P＜0．01）。福辛普利组和依贝沙坦组与安慰剂组相比平均动脉压下降、心室重量／体重及非心肌细胞增生数量下降，二合用与安慰剂组比较以上指标下降显（P＜0．01）；两药单用和合用与安慰剂组相比左室舒张末压下降（P＜0．05）。两药单独和联合应用均阻止了非梗死区胶原沉积（P＜0．01，与安慰剂组相比），两个单独用药组高于假手术组（P＜0．05），而联合治疗组与假手组间无统计学差异。福辛普利组、依贝沙坦组及二合用组三间各指标差异均无统计学意义。结论：福辛普利和依贝沙坦均可限制心肌梗死后心肌肥大、抑制左室非梗死区胶原沉积和非心肌细胞增生；二合用2周未见上述作用更显。

Effects of fosinopril, irbesartan and combined treatment on ventricular remodeling after myocardial infarction

Objective The purpose of this study was to compare the effects of fosinopril, irbesartan, and their combination on ventricular remodeling after myocardial infarction (MI) Methods MI was induced by ligating the left anterior descending coronary artery in the rats Twenty four hours after coronary ligation, rats were randomly divided into four groups and treated for 2 weeks (1) MI+placebo; (2) MI+fosinopril; (3) MI+irbesartan; (4)MI+fosinopril+irbesartan; (5) sham ligation: We examined: (1)mean blood pressure, left ventricular end diastolic pressure(LVEDP); (2)heart weight(HW)/body weight (BW) ratio; (3) interstitial collagen and nonmyocyte cellular proliferation within the noninfarct zone Results Placebo treated infarcted rats developed significant increase in LVEDP( P <0 05), HW/BW( P <0 01), collagen content ( P <0 01), and nonmyocyte cellular proliferation ( P <0 01) compared with sham ligation control In fosinopril and irbesartan treated rats HW/BW, nonmyocyte cellular proliferation and mean blood pressure decreased compared with those in placebo treated rats Combination therapy attenuated significantly the changes of these parameters (all P <0 01 vs placebo) Fosinopril, irbesartan, and combination therapy limited the increase in LVEDP( P <0 05 vs placebo) Fosinopril or irbesartan alone, and combination therapy prevented collagen desposition ( P <0 01 vs placebo). Fosinopril or irbesartan alone did not completely inhibit collagen desposition. ( P <0 05 vs Sham control), combination therapy normalized collagen content (p=NS vs sham control)within the noninfarct zone The differance of every parameter among fosinopril, irbesartan, and combination therapy did not reach statistical significance Conclusion The present study demonstrated that both fosinopril and irbesartan could equally limit myocardial hypertrophy, attenuate the development of myocardial interstitial fibrosis, and prevent nonmyocyte cellular proliferation in the noninfarcted LV, which were not more significant in combination therapy of two weeks