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目的对比强力霉素、氯沙坦及其合用对大鼠急性心肌梗死(AMI)左室重构的防治作用。方法461只雌性SD大鼠,其中30只设为假手术组(仅在冠脉下穿线,不结扎);另外431只大鼠行冠脉前降支结扎致AMI,术后24h存活的254只大鼠随机分为下列各组:(1)AMI对照组64只;(2)强力霉素组(30mg·kg-·1d-1)63只;(3)氯沙坦组(10mg·kg-1·d-1)62只;(4)强力霉素(30mg·kg-·1d-1)和氯沙坦(10mg·kg-1·d-1)合用组65只。依疗程不同,将上述各组再均随机分为1、2和4周3个亚组。给药满疗程后各组均行血流动力学测定、心脏标本固定和病理分析。结果最终157只大鼠获完整资料。AMI对照及3个治疗组各亚组间的梗死面积差异均无显著性(P>0.05)。与假手术组相比,AMI对照组的左室舒张末压(LVEDP)、实际和相对重量(LVAW和LVRW)在各时间亚组均显著增加(P<0.05,P<0.01,P<0.001),且LVEDP在4周比1和2周时升高更显著(P<0.01);而左室内压最大上升和下降速率及其与左室收缩压的比值仅在4周时显著降低(P<0.001)。与AMI对照组相比,强力霉素、氯沙坦及其合用3个治疗组的LVEDP在各时间亚组均显著降低(P<0.05,P<0.01,P<0.001);LVAW和LVRW仅在氯沙坦和合用组的2和4周亚组,以及强力霉素组的4周亚组显著减轻(P<0.05,P<0.01,P<0.001);而左室内压最大下降速率和左室内压最大上升和下降速率与左室收缩压的比值仅在3个治疗组的4周亚组显著增加(P<0.05,P<0.01)。上述各指标在3个治疗组的各时间亚组间差异均无显著性(P>0.05)。结论强力霉素和氯沙坦均能有效防治大鼠AMI左室重构,改善左室收缩和舒张功能,且作用相当,而两药合用似无叠加效应,值得进一步研究。
Objective To compare the preventive and therapeutic effects of doxycycline, losartan and their combination on left ventricular remodeling after acute myocardial infarction (AMI) in rats. Methods A total of 461 female Sprague-Dawley rats were randomly divided into three groups: sham-operated group (only percutaneous coronary artery was ligated without ligating); another 431 rats were performed AMI with ligation of the anterior descending coronary artery, 254 The rats were randomly divided into the following groups: (1) 64 AMI control groups; (2) 63 doxycycline groups (30 mg · kg -1 · d -1); (3) losartan group (10 mg · kg- 1 · d-1), and (4) 65 doxycycline (30 mg · kg-1d-1) and losartan (10 mg · kg-1 · d-1) According to the different course of treatment, the above groups were randomly divided into 1, 2 and 4 weeks 3 subgroups. After the course of drug administration, hemodynamics, heart specimen fixation and pathological analysis were performed in all groups. Results The final 157 rats were given complete information. There were no significant differences in infarct size between the AMI control group and the three treatment groups (P> 0.05). LVEDP, LVED and LVRW in the AMI control group were significantly increased at each time point (P <0.05, P <0.01, P <0.001) compared with the sham operation group , And LVEDP increased more significantly at 4 weeks than at 1 and 2 weeks (P <0.01). However, the ratio of left ventricular pressure to left ventricular systolic pressure was significantly lower at 4 weeks (P <0.001) . Compared with the AMI control group, LVEDP was significantly decreased in the three treatment groups (P <0.05, P <0.01, P <0.001) Losartan and combination group 2 and 4 weeks subgroup, and doxycycline group 4 weeks subgroup significantly reduced (P <0.05, P <0.01, P <0.001); and the maximum rate of decline in left ventricular pressure and left ventricular The ratio of maximum pressure rise and fall rate to left ventricular systolic pressure was significantly increased only in the 4-week subgroup of three treatment groups (P <0.05, P <0.01). There was no significant difference among the three subgroups in each treatment time (P> 0.05). Conclusion Both doxycycline and losartan can effectively prevent left ventricular remodeling in AMI rats and improve left ventricular systolic and diastolic function with similar effects. However, the combination of both drugs seems to have no additive effect and deserves further study.