普伐他汀不同给药时间对大鼠急性心肌梗死后心室重构的影响  

Effects of pravastatin on ventricular remodeling in rat after acute myocardial infarction at different administration times

作　　者：李晓波[1] 唐杨章[1] 

机构地区：[1]安徽省淮北市人民医院心血管内科,235000

出　　处：《中国现代医药杂志》2011年第2期26-30,共5页Modern Medicine Journal of China

摘　　要：目的①观察普伐他汀能否改善急性心肌梗死后的心室重构和心功能;②观察普伐他汀不同给药时间对改善心室重构的区别;③探讨普伐他汀改善心室重构和心功能的机制。方法制作大鼠急性心肌梗死模型并分组。将32只大鼠随机分成4组:A组假手术组、B组心肌梗死对照组、C组普伐他汀早期干预组、D组普伐他汀晚期干预组,每组8只。早期和晚期干预分别选择梗死后即刻和72小时后以普伐他汀(3mg/kg)灌胃,共持续8周,A、B组每日以等量水灌胃,其余喂养饲料相同。BL-420S生理机能实验系统记录ECG、LVSP、LVEDP、±dp/dtmax、HR、SBP、DBP。RT-PCR检测左心室非梗死区TNF-α、MMP-2、MMP-9的mRNA的表达。Western-blot测定左心室非梗死区TNF-α蛋白的表达。结果①血流动力学指标:4组的心率无明显变化;B、C、D组的LVEDP较A组有明显升高(P<0.01),SBP、DBP、LVSP、±dp/dtmax显著降低(P<0.01);C、D组的LVEDP显著低于B组(P<0.05),±dp/dtmax显著高于B组(P<0.05);C、D组与B组比较SBP、DBP、LVSP无明显变化。②TNA-αmRNA及蛋白表达:B、C、D组均比A组高(P<0.01),C、D组比B组低(P<0.05),C组比D组低(P<0.05)。③MMP-2、MMP-9的mRNA的表达:B、C、D组均比A组高(P<0.01),C、D组比B组低(P<0.05),C组比D组低(P<0.05)。结论①普伐他汀可以有效防治心肌梗死后心室重构。②普伐他汀防治心肌梗死后心室重构与用药时间有相关性,尤其是早期干预较晚期干预在防治心肌梗死后心室重构效果更佳。③普伐他汀主要通过减少MMP-2、MMP-9的mRNA的表达并且抑制TNA-αmRNA及蛋白表达达到防治心肌梗死后的心室重构。Objective ①To observe pravastatin amelioration on ventricular remodeling after acute myocardial infarction.②To observe pravastatin indiversity administ time amelioration on ventricular remodeling after acute myocardial infarction.③To explore pravastatin amelioration mechanism about ventricular remodeling. Methods ①Rats and infarction healthy female wistar rats, were randomized into four groups： group A was sham group（n=8）, group B was AMI control group（n=8）, rats in group C were treated with pravastatin（3mg/kg/d） after acute myocardial infarction for eight weeks, rats in group D were treated with pravastatin （3mg/kg/d） the third day into the eight weeks. In group B and group A were treated with drinking water. ②Hemodynamics analysis BL-420S physiological function experimental system was used to record ECG, LVSP, LVEDP, ±dp/dtmax, HR, SBP and DBP.③TNF-α, MMP-2,MMP-9, gene expression were determined by RT-PCR.④Myocardial TNF-α protein production was analyzed by western blotting. Results Hemodynamics analysis： in group B、C and D, LVEDP were significantly increased （P0.01）, while SBP、DBP、LVSP and ±dp/dtmax markedly decreased（P0.01）, and HR did not change compared with A group（P0.05）. Compared with group B,LVEDP significantly decreased in group C and D（P0.05）, ±dp/dtmax significantly increased （P0.05）, while SBP、DBP and LVSP had no significantly difference（P0.05）. MMPS gene expression and activity changes compared with group A, MMP-2 and MMP-9 gene expression and activity in group B,C and D markedly increased（P0.01）,group C and D displayed significant reductions in MMPS gene expression and activity compared with group B （P0.05）. In group B、C and D,TNF-α mRNA expression and protein production markedly increased（P0.01）. Compared with group B, C and D displayed significant reductions in both TNF-α mRNA and protein expression（P0.05）. Conclusion Early pravastatin treatment can attenuate the expression of MMP-2,9 in the non-infarcted

关 键 词：普伐他汀 大鼠 心肌梗死 心室重构 肿瘤坏死因子-Α 基质金属蛋白酶 

分 类 号：R542.22[医药卫生—心血管疾病]