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内质网应激与心血管疾病
  • ISSN号:1673-6583
  • 期刊名称:《国际心血管病杂志》
  • 时间:0
  • 分类:R361.1[医药卫生—病理学;医药卫生—基础医学]
  • 作者机构:[1]中国中医科学院西苑医院,北京100091, [2]解放军总医院病理生理研究室,北京100853
  • 相关基金:国际科技合作项目(No.2010DFA31690);国家自然科学基金资助项目(No.81070130)
中文摘要:

目的:研究西洋参茎叶总皂苷(Panax quinquefolium saponin,PQS)对大鼠急性心肌梗死(AMI)后心室重构的作用及其机制。方法:健康雄性SD大鼠90只,随机分为假手术(sham)组、AMI组、牛磺酸(300 mg.kg-1.d-1)组及PQS(50、100和200 mg.kg-1.d-1)组(n=15)。结扎大鼠左冠状动脉前降支复制AMI模型。术后第2天开始,各用药组用饮用水10 mL.kg-1.d-1溶解药物灌胃,sham组及AMI组予等量饮用水灌胃。术后4周,超声心动图检测左室结构及功能变化;TTC染色法测定心肌梗死范围;比色法测定非梗死区心肌组织羟脯氨酸含量;TUNEL法检测非梗死区心肌细胞凋亡率,Western blotting检测内质网应激分子葡萄糖调节蛋白78(GRP78)、钙网蛋白(CRT)、C/EBP同源蛋白(CHOP)及凋亡相关蛋白Bcl-2、Bax的表达。结果:与AMI组比较,PQS低、中、高剂量组左室收缩末期内径分别降低17.2%、20.3%和38.8%,左室舒张末期内径分别降低8.9%、9.0%和17.2%,左室收缩末期容积分别降低31.4%、38.5%和66.9%左室舒张末期容积分别降低18.2%、18.8%和34.2%,射血分数分别升高44.9%、60.1%和118.0%,左室短轴缩短率分别升高55.4%、71.0%和148.0%,梗死范围分别降低4.6%、39.5%和55.8%(均P〈0.05);非梗死区心肌组织羟脯氨酸含量分别降低34.5%、35.9%和48.7%(P〈0.01)。与AMI组比较,PQS 200 mg.kg-1.d-1组心肌细胞凋亡率降低27.3%(P〈0.05),GRP78和CRT蛋白表达分别降低79.9%和80.8%(P〈0.01),CHOP和Bax分别降低42.5%和53.1%(P〈0.01),Bcl-2表达升高1.1倍(P〈0.01);上述保护作用的程度与内质网应激抑制剂牛磺酸相近(P〉0.05)。Spearman相关分析发现CHOP蛋白表达与心肌细胞凋亡率显著正相关(r=0.797,P〈0.01)。结论:PQS剂量依赖性减轻大鼠心肌梗死后心室重构,其机制与抑制CHOP介导的内质网应激凋亡通路有关。

英文摘要:

AIM : To investigate the effect of Panax quinquefolium saponin (PQS) on ventricular remodeling after acute myocardial infarction (AMI) in rats and its mechanism. METHODS. Ninety healthy male SD rats were ran- domly divided into sham group, AMI group, taurine 300 mg · kg-1 · d-~1 group, PQS 50 mg· kg-1· d-1 group, PQS 100 mg · kg-1· d -1 group and PQS 200 mg· kg- 1 · d -1 group. AMI models were produced by ligating the left coronary arter- ies in SD rats. The rats in each treatment group were gavaged with drugs dissolved in water ( 10 mL ·kg-1 · d -1 ), and the rats in sham group and AM! group received equal volume of water. Four weeks after MI, the left ventricle fractional short- ening, ejection fraction and structure were evaluated by echocardiography. Myocardial infarct size was measured by 2,3,5- triphenyhetrazolium chloride staining. The hydroxyproline level was measured by eolorimetric method. Apoptosis of the car- diomyocytes was detected by TUNEL. In addition, the expression of endoplasmic reticulum stress-related molecules in the noninfarcted myocardium was determined by Western blotting. RESULTS: Comoared with AMI group, the left ventricularend-systolic dimension in PQS 50 mg ·kg-1 · d-1 group, PQS 100 mg · kg-1 · d-1 group and PQS 200 mg · kg-1 · d-1 group decreased by 17. 2%, 20. 3 % and 38.8% respectively, and the left ventricular end-diastolic dimension decreased by 8.91%, 8.95% and 17.20%, respectively. The left ventricular end-systolic volume decreased by 31.4%, 38. 5% and 67. 0%, respectively, and the left ventricular end-diastolic volume decreased by 18.2%, 18. 8% and 34.2%, respective- ly. The left ventricular ejection fraction increased by 44. 9%, 60. 1% and 118.0%, respectively,and the fractional short- ening increased by 55.4%, 71.0% and 148. 0%, respectively. The infarction size decreased by 4. 6%, 39. 5% and 55.8%, respectively,and the hydroxyproline level in noninfarcted myocardium decreased by 34. 5%, 35.9% and 48.7%, respectively. Compared with AMI group,

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期刊信息
  • 《国际心血管病杂志》
  • 中国科技核心期刊
  • 主管单位:上海市卫生和计划生育委员会
  • 主办单位:上海市医学科学技术情报研究所
  • 主编:赵强
  • 地址:上海市建国西路602号
  • 邮编:200031
  • 邮箱:xin_xg@yahoo.com.cn
  • 电话:021-33262055
  • 国际标准刊号:ISSN:1673-6583
  • 国内统一刊号:ISSN:31-1951/R
  • 邮发代号:4-188
  • 获奖情况:
  • 华东地区优秀期刊,中国期刊方阵“双效”期刊
  • 国内外数据库收录:
  • 中国中国科技核心期刊
  • 被引量:3405