醛固酮调控大鼠心肌钙调神经磷酸酶抑制因子的机制(PDF)
《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]
- 期数:
- 2005年第4期
- 页码:
- 317-319
- 栏目:
- 基础研究
- 出版日期:
- 2005-09-05
文章信息/Info
- Title:
- The mechanism of aldosterone regulated rat cardiac calcineurininhibitor
- Author(s):
- LI Zhaohui; XIE Xiaohua; LIU Li; CHEN Wen; CHANG Lianqing; DENG Zhaoyang
- General Hospital of PLA, Beijing 100853, China
- 关键词:
- 醛固酮; 钙调神经磷酸酶抑制因子
- Keywords:
- aldosterone; calcineurininhibitor
- 分类号:
- R335
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 目的 通过皮下注射醛固酮(Ald)，诱导大鼠心肌肥厚反应发生，采用蛋白印记杂交的方法，观察心肌组织钙调神经磷酸酶（CaN）抑制因子（Cain）表达的变化。方法 健康雄性Wistar大鼠，随机分为3组（n=7），①正常对照组；②心肌肥厚组：皮下注射Ald 18 μg·d-1，连续14 d；③螺内酯组：皮下注射Ald 18 μg·d-1，同时给予螺内酯20 mg·kg-1·d-1灌胃，亦连续14 d。采用大鼠尾动脉法测量平均动脉压，称重后抽血处死，分别计算左心室质量（LVW）及全心质量（HW）与体质量（BW）的比值。通过放免方法测定血浆Ald含量，运用蛋白印记杂交的方法，测定Cain表达的变化。结果 心肌肥厚组与正常对照组比较，BP显著升高，LVW/BW及HW/BW比值显著增加，血浆Ald增加，CaN活性增加，Cain的表达显著增加；而螺内酯组与心肌肥厚组比较，LVW/BW及HW/BW比值下降，血浆Ald增加，CaN活性减低，Cain的表达显著减少，而BP无明显变化。结论 外源性醛固酮可通过CaN依赖的信号转导通路诱导心肌肥厚反应的发生。同时，机体内源性Cain的表达的变化，受到CaN信号转导系统调控。
- Abstract:
- AIM To investigate the changes of myocardial calcineurin inhibitor (Cain) level in external aldosteroneinduced cardiac hypertrophic rats. METHODS Male Wistar rats were randomly divided into three groups: The control group, the Ald group treated with Ald (18 μg·d-1×14 d), and spironolactone group treated with Ald (18 μg·d-1×14 d) and the spironolactone (20 mg·kg-1·d-1×14 d). AngⅡ and Ald levels in plasma were determined by radioimmunoassay. The expression of myocardial Cain levels were determined by Western Blot. RESULTS The Ald level ,the expression of Cain and the activity of calcineurin in myocardium, all increased in the Ald group compared with the control group. And Ald level markedly increased in the spironolactone group compared with the Ald group; meanwhile, the expression of myocardial Cain and the activity of calcineurin decreased significantly. CONCLUSION External Ald induces cardiac hypertrophy through a calcineurindepedent signal pathway. The expression of internal Cain may be controlled by the activity of calcineurin.
参考文献/References
［1］ Zou Y, Hiroi Y, Uozumi H, et al. Calcineurin plays a critical role in the development of pressure overloadinduced cardiac hypertrophy［J］. Circulation, 2001,104: 97-101.
［2］ Rick B, Vega R, Beverly A, et al. Dual roles of modulatory calcineruininteracting protein 1 in cardiac hypertrophy［J］. Proc Natl Acad Sci USA, 2003,100: 669-674.
［3］ Taigen T, De Windt L, Lim HW, et al. Targeted inhibition of calcineurin prevents agonistinduced cardiomyocyte hypertrophy［J］. Proc Natl Acad Sci USA, 2000,97:1196-1201.
［4］符民桂，唐朝枢. 钙调神经磷酸酶活性测定［J］. 中国动脉硬化杂志，2000，8：82-83.
［5］De Windt L, Lim HW, Bueno OF, et al. Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo［J］. Proc Natl Acad Sci USA, 2001,98:3322-3327.
［6］Bueno OF, Wilkings BJ, Tymitz KM, et al. Impaired cardiac hypertrophic response in calcineurin Aβdeficient mice［J］. Proc Natl Acad Sci USA, 2002,99: 4586-4591.
［7］ Sakata Y, Masuyama T, Yamamoto K, et al. Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats［J］. Circulation, 2000, 102:2269-2275.
备注/Memo
- 备注/Memo:
- 收稿日期：2005-02-23.基金项目:“十五”军队医药卫生科研基金重点课题资助(No. 02Z0010)
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