盐皮质激素受体在Dahl盐敏感大鼠心肌纤维化中的作用
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(南京医科大学附属常州市第二人民医院心内科,江苏省常州市 213003)

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朱傲霜,博士,副主任医师,主要从事高血压的发病机制研究,E-mail为1579896672@qq.com。

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常州市卫生局重大科技项目(ZD201012)


Role of Mineralocorticoid Receptor in Myocardial Fibrosis of Dahl Salt-sensitive Hypertensive Rats
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The Affiliated Hospital of Nanjing Medical University, Changzhou No 2 Hospital, Changzhou, Jiangsu 213003,China)

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    摘要:

    目的 探讨心肌组织中盐皮质激素受体(MR)在高血压大鼠心肌纤维化中的作用。方法 通过高盐饮食以及加用选择性盐皮质激素受体拮抗剂依普利酮干预Dahl盐敏感大鼠血压,8周后通过心脏/体重比值、心肌组织AZAN染色以及定量PCR检测心肌组织胶原蛋白mRNA评估心肌纤维化水平,蛋白印迹法检测大鼠心肌组织盐皮质激素受体的表达水平以及定量PCR检测心肌组织炎症相关因子PAI-1和TGF-β1 mRNA的表达水平,评价盐皮质激素受体和心肌纤维化的关系。结果 和低盐饮食组比较,高盐饮食诱导Dahl盐敏感大鼠血压升高[168.1±10.8 mmHg比124.3±10.2 mmHg],心脏/体重比值明显增加[(0.341±0.006)比(0.287±0.004)],大鼠心肌组织纤维化比例[(11.78%±0.54%)比(3.12%±0.55%)]和胶原蛋白ⅣmRNA[(3.23±0.21)比(1.32±0.06)]表达均增加;大鼠心肌组织盐皮质激素受体的表达水平增加[(0.38±0.03) 比(0.21±0.07)];心肌组织 PAI-1和TGF-β1 mRNA的表达水平增加[PAI-1:(0.88±0.12)比(0.55±0.18);TGF-β1:(2.25±0.37)比(1.26±0.41)],而且同心肌组织纤维化呈正相关。利用选择性盐皮质激素受体拮抗剂依普利酮后大鼠心脏/体重比值、心肌纤维化比例、胶原蛋白mRNA、盐皮质激素受体、PAI-1和TGF-β1 mRNA均明显下降。结论 盐皮质激素受体和相应的激素相互作用,介导心肌炎症,引起心肌组织纤维化。盐皮质激素受体拮抗剂可以缓解高血压引起的心肌纤维化,改善心肌重构。

    Abstract:

    Aim To investigate the role of mineralocorticoid receptor (MR) in myocardial fibrosis of Dahl salt-sensitive hypertensive rats. Methods Dahl salt-sensitive hypertensive rats were treated with high-salt diets or combined with eplerenone (100 mg/kg per day, orally) for 8 weeks. Then measured blood pressure, heart weight/body weight ratios, assessed myocardial fibrosis level by myocardial tissue AZAN staining and quantification of collagen IV mRNA, and also detected the expression of mineralocorticoid receptor protein by Western blot and inflammation related factor in myocardial tissue such as PAI-1 and TGF-β1 mRNA expression by Real Time PCR, then analysied the relationship of the expression of mineralocorticoid receptor and myocardial fibrosis. Results Dahl salt-sensitive rats fed with a high salt diet had increased blood pressure [(168.1±10.8) mmHg vs(124.3±10.2)mmHg]and heart weight/body weight ratio[(0.341±0.006)vs(0.287±0.004)]. The percentage of myocardial fibrosis(11.78%±0.54% vs 3.12%±0.55%)and collagen Ⅳ mRNA(3.23±0.21 vs 1.32±0.06)expression were increased in myocardial tissue. The expression of MR protein and PAI-1,TGF-β1 mRNA were also increased in myocardial tissue, PAI-1 and TGF-β1 mRNA expression were positively related with myocardial fibrosis. Combined with eplerenone in diet, following parameters including blood pressure, heart weight/body weight ratios, myocardial fibrosis level, MR protein, mRNA of collagen, PAI-1 and TGF-β1 were decreased. Conclusion Interaction of MR and corresponding hormone, can induce inflammatory reaction in heart and result in myocardial fibrosis. MR antagonists can relieve myocardial fibrosis induced by hypertension,and improve myocardial remodeling.

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朱傲霜,张宇燕,丁志坚,陈解忠,刘宇.盐皮质激素受体在Dahl盐敏感大鼠心肌纤维化中的作用[J].中国动脉硬化杂志,2016,24(6):566~570.

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  • 收稿日期:2015-07-08
  • 最后修改日期:2015-09-28
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  • 在线发布日期: 2016-06-30