目的:探讨黄芪皂苷甲(AsⅣ)对压力过载型左心室肥厚大鼠肾素-血管紧张素系统过度激活的影响。方法:采用缩窄大鼠腹主动脉制备压力过载所致的左心室肥厚模型。造模12周后分别给予灌服黄芪皂苷甲(1.0,3.3 mg.kg-1)12周。给药结束后,应用...目的:探讨黄芪皂苷甲(AsⅣ)对压力过载型左心室肥厚大鼠肾素-血管紧张素系统过度激活的影响。方法:采用缩窄大鼠腹主动脉制备压力过载所致的左心室肥厚模型。造模12周后分别给予灌服黄芪皂苷甲(1.0,3.3 mg.kg-1)12周。给药结束后,应用形态测量学测定左室质量指数;采用ELISA法测定大鼠血浆血管紧张素Ⅱ(AngⅡ)、醛固酮(A ld)含量和心肌组织AngⅡ含量;采用Real tim e PCR测定心肌组织ACE,AT1和AT2mRNA含量;采用W estern b lot法测定心肌组织AT1和AT2的蛋白表达。结果:与模型组相比,黄芪皂苷甲能降低左室质量指数;生化测定结果表明,模型组血浆AngⅡ和A ld含量较假手术组明显增加,心肌组织的AngⅡ含量也较假手术组显著提高。黄芪皂苷甲能降低模型组血浆AngⅡ和A ld含量以及心肌组织的AngⅡ含量;黄芪皂苷甲具有下调模型动物心肌组织血管紧张素转化酶(ACE)的基因表达,上调模型动物心肌组织AT2的基因和蛋白表达,但对模型动物心肌组织中上调的AT1基因和蛋白表达无逆转作用。结论:黄芪皂苷甲能够抑制压力过载型心肌肥厚大鼠肾素-血管紧张素系统的过度激活,这可能是其逆转左室肥厚的途径之一。展开更多
Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with ca...Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.展开更多
文摘目的:探讨黄芪皂苷甲(AsⅣ)对压力过载型左心室肥厚大鼠肾素-血管紧张素系统过度激活的影响。方法:采用缩窄大鼠腹主动脉制备压力过载所致的左心室肥厚模型。造模12周后分别给予灌服黄芪皂苷甲(1.0,3.3 mg.kg-1)12周。给药结束后,应用形态测量学测定左室质量指数;采用ELISA法测定大鼠血浆血管紧张素Ⅱ(AngⅡ)、醛固酮(A ld)含量和心肌组织AngⅡ含量;采用Real tim e PCR测定心肌组织ACE,AT1和AT2mRNA含量;采用W estern b lot法测定心肌组织AT1和AT2的蛋白表达。结果:与模型组相比,黄芪皂苷甲能降低左室质量指数;生化测定结果表明,模型组血浆AngⅡ和A ld含量较假手术组明显增加,心肌组织的AngⅡ含量也较假手术组显著提高。黄芪皂苷甲能降低模型组血浆AngⅡ和A ld含量以及心肌组织的AngⅡ含量;黄芪皂苷甲具有下调模型动物心肌组织血管紧张素转化酶(ACE)的基因表达,上调模型动物心肌组织AT2的基因和蛋白表达,但对模型动物心肌组织中上调的AT1基因和蛋白表达无逆转作用。结论:黄芪皂苷甲能够抑制压力过载型心肌肥厚大鼠肾素-血管紧张素系统的过度激活,这可能是其逆转左室肥厚的途径之一。
基金supported by High School Science and Technology Fund Planning Project of Tianjin Municipality,China(No.20060206)the Scientific Research Fund of Tianjin Medical University,China(No.2011ky33)
基金supported by the National Natural Science Foundation of China (81530009 to Youyi Zhang, 81670205 to Han Xiao)
文摘Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.
