黄芪甲苷对血管紧张素Ⅱ诱导大鼠心肌细胞肥大的抑制作用  

Inhibition effects of astragaloside Ⅳ on angⅡ-induced myocardial hypertrophy in neonatal rats

作　　者：杨光宇[1,2] 王洪新[1] 赵素玲[1] 梁灵君[1] 孙雪芳[1] 李洪秀 

机构地区：[1]辽宁医学院药理教研室,锦州121001 [2]盘锦市中心医院,盘锦124000

出　　处：《中药药理与临床》2013年第3期28-31,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然基金资助项目(30973898/C190702);辽宁省高等学校优秀人才支持计划(2008RC33)

摘　　要：目的:探讨黄芪甲苷(astragalosideⅣ,As-Ⅳ)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的乳鼠心肌细胞肥大的作用及机制。方法:以原代培养乳鼠心肌细胞为模型,血管紧张素Ⅱ0.1μmol/L诱导心肌细胞肥大。观察黄芪甲苷3μmol/L、10μmol/L、30μmol/L浓度对心肌肥厚的抑制作用,并进一步探索在钙调素激酶Ⅱ(CaMKⅡ)特异性抑制剂KN93及血管紧张素Ⅱ拮抗剂Losartan存在的情况下,对心肌肥厚的作用。用Lowry法测心肌细胞蛋白含量;消化分离法及计算机图像分析系统测细胞体积;以Fura-2/AM为荧光探针,采用Till阳离子测定系统,观察胞内[Ca2+]i瞬间变化;Western blot法测心肌细胞内CaMKⅡδB表达。结果:与正常组比,血管紧张素Ⅱ0.1μmol/L组心肌细胞总蛋白含量增加了61.4%,体积增大了88.6%,心肌细胞内[Ca2+]i静息水平提高,CaMKⅡδB的表达明显增加;洛沙坦1μmol/L及钙调素激酶Ⅱ特异性抑制剂0.2μmol/L明显抑制了血管紧张素Ⅱ诱导的上述改变。结论:黄芪甲苷对血管紧张素Ⅱ诱导的乳鼠心肌细胞肥大有抑制作用,其机制可能与降低[Ca2+]i及CaMKⅡδB表达有关。Objective：To investigate the effects and mechanism of AngⅡ-induced neonatal rat cardiomyocyte hypertrophy by astragaloside Ⅳ（AsIV）.Methods： The primary cultures of neonatal rat ventricular myocytes were used as models,the hypertrophic cardiac myotecytes were induced by AngⅡ0.1 μmol/L,observing the inhibitory effect of 3 μmol/L,10 μmol/L,30 μmol/L of As-IV and further exploration the effects in the calmodulin kinase II（CaMK II） in the presence of specific inhibitor KN93 and AngⅡantagonist Losartan on cardiac hypertrophy.Total protein content was assayed by Lowry method;the size of cardiomyocytes was measured by computer photograph analysis system;[Ca2 ＋]i transient was measured by Till image system by cell-loading Fura-2/AM.The expression of calmodulin dependent kinaseⅡ（CaMK Ⅱ） δB was determined by Western blot.Results： Compare with normal group,AngⅡ increased the total protein content and cell volume by 61.4%,88.6%（P 0.01）,and can significantly increased the augmentation of the spontaneous Ca2 ＋ transients and the expression of CaMKⅡδB.Los 1 μmol/L and KN93 0.2 μmol/L can significantly reduced these changes.Conclusion： Astragaloside Ⅳ can abolish the hypertrophic response induced by AngⅡ,which was partially via attenuating the augment of [Ca 2 ＋ ]i and the expression of CaMKⅡδB.

关 键 词：黄芪甲苷 血管紧张素Ⅱ 心肌肥大 钙浓度 钙调素激酶Ⅱ 

分 类 号：R285[医药卫生—中药学]