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目的:比较不同剂量卡维地洛对大鼠冠状动脉微栓塞(CME)后心室重塑的影响。方法:利用大鼠自体的血栓微粒造成心肌内小冠状动脉栓塞,建立CME模型。40只大鼠随机分成4组,即假手术组(SO组)、CME组、小剂量卡维地洛组(LCAR组,1.0 mg·kg-1·d-1)和大剂量卡维地洛组(HCAR组,10.0 mg·kg-1·d-1)。灌胃4周后,行心功能检测、血流动力学测定及心肌病理学分析。结果:与SO组比较,CME组细胞间质胶原容积分数(CVF)与心肌细胞凋亡率(Rapo)明显增加,左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)明显增大,左心室短轴缩短率(LVFS)、左心室射血分数(LVEF)明显降低(均P<0.01);左心室舒张末期压(LVEDP)明显增加,左心室收缩压(LVSP)和左心室腔内压力最大上升速率(+LVdp/dt max)显著下降(均P<0.01)。与CME组比较,LCAR组和HCAR组心肌间质CVF和Rapo显著降低,LVEDD、LVESD明显减小,LVFS明显上升,LVEF明显改善(均P<0.01);LVEDP明显下降,+LVdp/dt max显著上升,心率明显减慢(均P<0.01)。除LVSP外,以上改变HCAR组均较LCAR组明显(P<0.05)。结论:①大鼠CME后心脏发生慢性重塑;②卡维地洛剂量依赖性地改善CME后心室重塑。
Objective: To compare the effects of different doses of carvedilol on ventricular remodeling after coronary micro-embolism (CME) in rats. Methods: Small coronary embolism was induced by thrombus particles in rats and CME model was established. Forty rats were randomly divided into four groups: sham operation group (SO group), CME group, low dose carvedilol group (LCAR group, 1.0 mg · kg -1 · d -1) and high dose carvedilol Group (HCAR group, 10.0 mg · kg-1 · d-1). Four weeks after gavage, cardiac function tests, hemodynamics and cardiomyopathological analysis were performed. Results: Compared with the SO group, the interstitial collagen volume fraction (CVF) and the cardiomyocyte apoptotic rate (Rapo) in CME group were significantly increased, and the left ventricular end diastolic dimension (LVEDD) and left ventricular end-systolic dimension diameter (LVESD) Left ventricular systolic pressure (LVFS), left ventricular ejection fraction (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (all P <0.01); left ventricular end diastolic pressure (LVEDP) The maximum rate of increase of internal pressure (+ LVdp / dt max) decreased significantly (all P <0.01). Compared with CME group, CVF and Rapo of myocardial interstitial in LCAR group and HCAR group were significantly decreased, LVEDD and LVESD were significantly decreased, LVFS and LVEF were significantly improved (all P <0.01), LVEDP and + LVdp / dt max were significantly decreased Rise, heart rate was significantly slowed (both P <0.01). Except for LVSP, the changes in HCAR group were more significant than those in LCAR group (P <0.05). CONCLUSION: ①Cytocardial remodeling occurs after CME in rats. ② Carvedilol improves the remodeling of CME in a dose-dependent manner.