益气活血中药对急性心肌梗死后大鼠心肌线粒体生物合成相关蛋白的影响

摘要

目的 观察益气活血中药西洋参茎叶总皂苷(PQS)和精制血府胶囊配伍对急性心肌梗死(AMI)大鼠心肌AMPK活化的线粒体生物合成相关蛋白的影响.方法 SD雄性大鼠60只,高脂饲料喂养28 d,4%水合氯醛麻醉后,结扎冠状动脉前降支造成AMI模型,成活大鼠共26只,随机分为模型组和益气活血组,每组13只;并设假手术组(只穿刺,不结扎)13只.术后2 d开始灌胃药物,益气活血药液中包含了PQS和精制血府浸渍膏,药物灌胃剂量为PQS 162 mg/ (kg·d),精制血府3.6 mg/ (kg·d),模型组和假手术组大鼠灌胃等量的蒸馏水.灌胃28 d后,将大鼠麻醉,行超声心动图检测,测定大鼠左室收缩末内径(LVDs)、左室舒张末内径(LVDd)、射血分数(EF).完成后,打开大鼠胸腔,取出心脏,进行心肌病理组织学检测及心肌组织内AMP激活蛋白激酶ɑ2(AMPKɑ2)、过氧化物酶体增生物激活的受体γ共激活因子1ɑ(PGC1ɑ)基因和蛋白的测定.结果 心脏超声结果显示:与假手术组相比,模型组大鼠LVDs、LVDd值显著增大(P<0.05),EF值显著下降(P<0.05);与模型组相比,益气活血组大鼠LVDs、LVDd值均降低(P<0.05),EF值升高(P<0.05).RT-PCR结果显示:与假手术相比,模型组大鼠心肌组织内AMPKα2、PGC1α基因表达下调(P<0.05);与模型组相比,益气活血组心肌组织内AMPKα2、PGC1α基因上调(P<0.05).Western结果:与假手术相比,模型组大鼠心肌组织内AMPKα2、PGC1α蛋白表达下调(P<0.05);与模型组相比,益气活血药物组心肌组织内AMPKα2、PGC1α蛋白表达上调(P<0.05).结论 益气活血中药可改善AMI后左室功能,抑制AMI后左室重构,该作用可能与促进线粒体生物合成蛋白(AMPKα2、PGC1α)的表达有关.%Objective To observe the effect of strengthing qi and activating blood Chinese medicine Panax quinquefolius saponin (PQS) and refined Xuefu Capsules on AMPK activated-mitochondrial biogenesis protein in rats myocardium after acute myocardial infarction (AMI).Methods Sixty male Sprague-Dawley (SD) rats, fed with high-fat diet for 28 d, after anesthetized with 4% chloral hydrate, 26 of them were made as AMI model successfully by descending artery ligation.And all of AMI model rats were randomly divided into model group, strengthing qi and activating blood Chinese medicine group, for 13 rats in each group.And set 13 rats as sham group (only puncture,without ligation).The rats of strengthing qi and activating blood Chinese medicine group were gavaged with the strengthing qi and activating blood Chinese medicine, with PQS was given 162 mg/(kg·d),refined Xuefu capsules was given 3.6 mg/(kg·d) since the next day of surgery.At the same time, the rats of model group and sham group are gavaged with equal amount of distilled water.After 28 d, the rats were anesthetizedto measure left ventricular end-systolic inner diameter(LVDs), left ventricular end-diastolic diameter(LVDd), ejection fraction(EF)by Ultrasonic echocardiography.When finished, the chest was opened, and the hearts was removed for histopathology testing and the gene and protein of AMP-activated protein kinase α2 (AMPKα2), Peroxisome proliferator-activated receptor-γ co-activator1α (PGC1α) in rats myocardium testing.Results Echocardiography showed that compared with sham group, LVDs and LVDd value in model group significantly increased (P<0.05) and EF values decreased significantly(P<0.05).Compared with the model group, the LVDs and LVDd value in strengthing qi and activating blood Chinese medicine group reduced obviously (P<0.05) and EF value in strengthing qi and activating blood Chinese medicine group increased obviously (P<0.05).RT-PCR showed that compared with sham group, AMPKα2 and PGC1α genes of myocardial tissues in model group down-regulated (P<0.05).Compared with the model group, AMPKα2 and PGC1α genes of myocardial tissues in strengthing qi and activating blood Chinese medicine group up-regulated (P<0.05).Western Blot showed that compared with sham group, protein expression of AMPKα2 and PGC1α of myocardial tissues in model group down-regulated (P<0.05).Compared with the model group, protein expression of AMPKα2 and PGC1α of myocardial tissues in strengthing qi and activating blood Chinese medicine group up-regulated (P<0.05).Conclusion Strengthing qi and activating blood Chinese medicine can inhibit left ventricular remodeling, and improve left ventricular function after AMI.The role of protection may related to the promotion of mitochondrial biogenesis protein (AMPKα2 and PGC1α) expression in myocardium after AMI.