摘要
目的观察瑞舒伐他汀对新西兰大白兔心肌梗死后心室重构的影响,并探讨其可能机制。方法 45只雄性新西兰大白兔随机分成3组,假手术组(S组,n=15),心肌梗死对照组(MI组,n=15),瑞舒伐他汀干预组(R组,n=15)。MI组和R组大鼠结扎左冠状动脉前降支建立急性心肌梗死模型。MI组及S组术后24 h灌等量的生理盐水。R组于术后24 h直接灌胃法给药,给药剂量以10 mg/(kg·d)计算。干预2周后,进行心脏超声测定,然后随即处死新西兰大白兔,取出心脏,通过TUNEL法检测心肌梗死边缘区的细胞凋亡率,使用流式细胞仪法测定心肌梗死边缘区Caspase-3的表达,同时应用Western blot方法检测p38、p-p38在此区域的表达。结果 R组兔的左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)较MI组减小,而左室射血分数(LVEF)较MI组增高;R组及MI组兔心肌梗死边缘区的心肌细胞凋亡率均高于S组,而R组兔的心肌细胞凋亡率低于MI组;R组兔心肌梗死边缘区与MI组p38表达比较未见明显差异,而前者Caspase-3及p-p38表达低于后者,差异具有统计学意义(P<0.05)。结论瑞舒伐他汀可抑制心室重构及改善心脏功能,其机制可能是通过抑制p38的磷酸化从而阻止Caspase-3的活化,最终抑制心肌细胞凋亡。
Objective To investigate the effects of rosuvastatin on ventricular remodeling after myocardial infarction and the potential mechanism.Methods Forty-five male New Zealand albino rabbits were randomly divided into three groups: sham operation(S) group(n = 15),myocardial infarction(MI) group(n = 15) and rosuvastatin intervention(R) group(n = 15).AMI animal models were established with the ligation of left anterior descending coronary artery in MI group and R group.Rabbits in R group were administered with rosuvastatin at a dose of 10mg /(kg·d) via direct gastric gavage 24 hours after the ligation;while rabbits in the other two groups were administered with same volume of distilled water via gastric gavage at the same time.After two weeks,all the rabbits were killed,and the hearts were taken out to detect apoptosis by TUNEL.The expression of Caspase-3 at the myocardial infarction edge area was measured by flow cytometry,and the expressions of p38,p-p38 in protein level were measured by western blot.Results Compared with MI group,the left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) in R group were smaller,but the left ventricular ejection fraction(LVEF) was higher.There was no significant difference between R group and MI group in the expression of p38.However,there were significant differences in Caspase-3 and p-p38 expression in the tissue of the myocardial infarction edge area between R group and MI group.Conclusions Rosuvastatin may suppress ventricular remodeling and improve cardiac function by preventing cardiomyocyte apoptosis through restraining phosphorylation of p38 and preventing Caspase-3 activation.
出处
《实用老年医学》
CAS
2013年第9期729-733,共5页
Practical Geriatrics
关键词
瑞舒伐他汀
心肌梗死
心室重构
细胞凋亡
rosuvastatin
myocardial infarction
ventricular remodeling
apoptosis
