摘要
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 effects of doxycycline, losartan, and their combination in the prevention of left ventricular remodeling （LVRM） after acute myocardial infarction （AMI） in rats. Methods Twenty-four hours after the induction of AMI, the 254 survival rats were randomly assigned to the following groups and received drug treatment： （1） AMI controls （n = 64）, （2） doxycycline （30 mg·kg^-1·d^-1, n=63）, （3） losartan （10 mg·kg^-1·d^-1, n=62）, and （4） combination doxycycline and losartan （30 and 10 mg·kg^-1·d^-1 respectively, n= 65） treatment groups. Also, sham operated rats （n= 30） were selected randomly. Each group was further divided into three subgroups of 1, 2, and 4 weeksof treatment. After the completion of treatment, hemodynamic studies were performed. Then, the heart of rat was fixed and analyzed pathologically. Results Exclusive of the dead rats and the hearts with the myocardial infarction size 〈 35% or 〉 50%, complete experimental data were obtained in 157 rats. Besides sham operated rats, there was no significant difference in myocardial infarction sizes among the 12 subgroups of AMI control and drug treatment groups （P 〉 0.05）. Compared with sham operated rats, left ventricular end diastolic pressure （LVEDP） and left ventricular absolute weight and relative weight （LVAW and LVRW） were significantly increased in 1, 2, and 4 week subgroups of AMI controls （P〈 0.05, P〈 0.01, and P 〈 0.001, respectively）, with LVEDP elevated more significantly in 4 week than in 1 and 2 week subgroups （P〈0.01）; whereas the maximum rising and dropping rate of left ventricular pressure （±dp/dt） and its corrected value by left ventricular systolic pressure （±dp/dt/LVSP） were all significantly decreased only at 4 week subgroup of AMI controls （P 〈 0.001 ）. Compared with AMI controls group, LVEDP was significantly decreased in all 1, 2, and 4 week subgroups of the three treatment groups （P 〈 0.05, P 〈 0.01, and P 〈 0.001, respectively）; LVAW and LVRW were significantly decreased in 2 and 4 week subgroups of losartan and combination groups （P 〈 0.05, P 〈 0.01, P〈 0.001, respectively）, and in only 4 week subgroup in doxycycline （P〈0.05, P〈0.01, and P 〈 0.001, respectively）; whereas the maximum dropping rate of left ventricular pressure and the corrected value of left ventricular pressure rising and dropping rate were significantly increased only in 4 week subgroups of all three treatment groups （P 〈 0.05, P 〈 0.01, respectively）. There is no significant difference in all indices above among the three treatment groups at all three time points （P 〉 0.05）. Conclusion It is indicated that doxycycline can prevent left ventricular remodeling and improve its systolic and diastolic function after AMI in rats, with the equivalent effect to that of losartan. There seems no additive effect when the two drugs are used in combination.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2005年第4期479-485,共7页
Acta Academiae Medicinae Sinicae
基金
国家高科技研究发展计划项目(863项目)(102-08-02-05)~~
关键词
心肌梗死
左室重构
强力霉素
氯沙坦
myocardial infarction
left ventricular remodeling
doxycycline
losartan
