大、中、小剂量依那普利防治大鼠急性心肌梗塞左心室重构的作用对比

Comparison of Effects of High,Middle and Low Doses of Enalapril in Prevention of Left Ventricular Remodeling after Acute Myocardial Infarction in Rats

目的：对比大、中、小剂量依那普利对大鼠急性心肌梗塞（ＡＭＩ）左心室重构的防治作用，并评价其量效关系。 方法：ＡＭＩ术后４８小时存活的９７只雌性ＳＤ大鼠随机分成：ＡＭＩ对照以及依那普利大、中、小剂量［１０ｍｇ／（ｋｇ·ｄ）、１ｍｇ／（ｋｇ·ｄ）和０．１ｍｇ／（ｋｇ·ｄ）］４组。另设：假手术组和正常组作对照。给药治疗４周后均行血液动力学测定、心脏标本固定及病理分析。最终６７只大鼠获完整资料，在上述各组中的数目分别为１３、１３、１２、１２、８和９只。 结果：ＡＭＩ各组间梗塞面积均无显著差异（４５．４％～４７．４％，Ｐ均＞００５）。与假手术组相比，ＡＭＩ对照组左心室舒张末压、容积以及实际和相对重量均显著增加（Ｐ均＜０．００１＝，发生了左心室重构；而左心室内压最大上升下降速率（±ｄｐ／ｄｔ）及其校正值［±ｄｐ／ｄｔ／左心室收缩压（ＬＶＳＰ）］均显著降低（Ｐ＜０．０１～０．００１＝。与ＡＭＩ组相比，依那普利大、中、小剂量３治疗组的左心室舒张末压、容积以及实际和相对重量均显著降低或减小（Ｐ＜０．０５～０．００１），且左心室舒张末压、容积和实际重量在大剂量组比小剂量组降低或减小更显著（Ｐ均＜０．０５＝；而±ｄ?

Objectives:To compare the effects of high,middle and low doses of enalapril in the prevention of left ventricular remodeling(LVRM)after acute myocardial infarction(AMI)in rats,and to evaluate the dose effect relation. Methods:AMI were made by ligating left coronary artery in female SD rats.Forty eight hours after the procedure,97 survivivors were randomized to one of the following four groups of AMI controls and high ,middle and low dose enalapril[10mg/(kg·d),1mg/(kg·d) and 0 1mg/(kg·d) respectively].Sham operated(n 13)and normal rats(n=10)were selected randomly to serve as non infarction controls.Enalapril was delivered by direct gastric gavage.After 4 weeks of treatment,hemodynamic studies were performed.And then the rat hearts were fixed with 10% formalin and pathologic analysis was conducted in each groups.Complete experimental data were obtained in 67 rats,which were comprised of ① AMI controls(n=13),②high dose enalapril group(n=13),③middle do se enalapril group(n=12),④low dose enalapril group(n=12),⑤sham operated group(n=8)and ⑥mormal controls(n=9). Results:There were no significant diff erences among the four AMI groups in MI size (45.4%-47.4%,all p>0.05).Compared with the sham operated rats,the left ventricular(LV)end diastolic pressure(LVEDP),volume(LVV)and absolute and relative weight(LVAW and LVRW) in AMI group were all significantly inc reased (all p<0.001=,indicating LVRM had developed after AMI.The maximum left ventricular pressure rising and dropping rates(±dp/dt) and their LV systolic pressure corrected values(±dp/dt/LVSP) were all significantly reduced in AMI group(p<0.01-0.001).Compared with AMI group,LVEDP,LVV,L VAW and LVRW were all significantly decr eased in three enalapril groups(p< 0.05-0 001).The reduction of LVEDP,LVV,and LVAW was more significant in high dose than in low dose enalapril group (all p<0.05=.The ±dp/dt/LVSP w ere significantly improved only in high and middle dose enalapril groups(p <0.05-0.01=. Conclusions:①High,middle and low doses of enalapril are all effective in preventing left ventricular remodeling after AMI in rats,with high dose being more effective.②Both high and mid dle doses of enalapril can also improve LV systo diastolic function,with low dose of enalapril was found ineffective.