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醛固酮诱导大鼠相关器官组织钙调神经磷酸酶的活化(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2005年第4期
页码:
320-322
栏目:
基础研究
出版日期:
2005-09-05

文章信息/Info

Title:
The activation of the tissue calcineurin induced by the aldosterone in the partial organs of Wistar rats
作者:
谢晓华1; 陈雯1; 常连庆2; 李朝晖1; 李晓玲1; 高银杰1; 刘宁3; 唐朝枢4
1．解放军总医院南四科，北京 100853；2．军医进修学院；3．天津解放军第272医院；4．北京大学医学部
Author(s):
XIE Xiaohua1;  CHEN Wen1;  CHANG Lianqing2;  LI Zhaohui1; LI Xiaoling1;  GAO Yinjie1;  LIU Ning3;  TANG Chaoshu4
1. General Hospital of PLA, Beijing 100853, China
关键词:
器官; 醛固酮; 钙调神经磷酸酶; 一氧化氮; 螺内酯
Keywords:
organs;  aldosterone;  calcineurin;  endothelin;  nitrogen monoxide; spironolactone
分类号:
R335
DOI:
-
文献标识码:
A
摘要:
目的 阐明醛固酮对重要器官组织细胞内信号分子钙调神经磷酸酶（CaN）的活化作用及其调控机制。方法 取雄性 Wistar大白鼠21只，分成醛固酮（Ald）组以Ald 18mg/d腹腔内注射4周，螺内酯组以Ald处理同时予螺内酯20 mg·kg-1·d-1灌胃4周及正常对照组。以放免法测得血Ald、血管紧张素II（AngII）和内皮素（ET）浓度；以硝酸盐法测定血NO浓度；以改良底物发色法测得心、脑、脾、肝、肺、肾和主动脉组织CaN活性。结果 醛固酮处理后，大鼠重要脏器的组织CaN活性均升高，分别为心147%、肺95%、脾65%和脑43%，与对照组比较，心、肺、脾和脑组织CaN活化达到统计学意义；血醛固酮浓度较对照组上升了1.62倍；血NO3-浓度明显下降；血中Ald/ NO3-上升了2.95倍， ET/NO3-和AngII/ NO3-分别上升了0.32倍和0.25倍。以螺内酯干预后，心、肺、脾、脑、肝组织CaN活化程度明显减轻；对大鼠血醛固酮浓度无显著影响，但血AngⅡ浓度下降、NO3-浓度明显升高；Ald/NO3-、ET/ NO3-、AngII/NO3-均明显下降。结论 外源性醛固酮可明显升高血中Ald/NO3- 浓度比，并显著活化心、肺、脾、脑组织CaN。螺内酯则可全面维护内皮活性因子稳态，下调血Ald/NO3-、AngII/NO3-和ET/NO3-比值，减轻组织CaN的活化效应。
Abstract:
AIM To detect the role of aldosterone(Ald) on the activation of rat tissue calcineurin (CaN) and underlying mechanism. METHODS 21 male wistar rats were randomly divided into 3 groups: Ald group(7 rats), treated with peritoneal injection (i.p) of Ald 18 μg/d for 4 wks ; spironolactone (spiron) group (7 rats), treated with Ald and with spiron 20 mg·kg-1·d-1 given orally for 4 wks; and control group (7 rats). The plasma concentrations of ald, angiotensin II（AngII）and endothelin（ET）, blood levels of NO, the tissue activities of the CaNs of the heart, lung, spleen, brain, kidney, liver and aortery were examed in the rats by radioimmunoassay, nitrate assay, and chromophoric assay , respectively. RESULTS The concentration of the plasma Ald increased by 1.62 times, the blood NO3- concentration was deceased, the ratio of Ald to NO3-( Ald/ NO3- ) increased by 2.95 times, and the cardiac,lung, spleen and brain tissue levels of CaN activities were 1.47, 0.95, 0.65 and 0.43 times higher respectively, in the rats treated with Ald than those in the normotensive rats(all P<0.05 or 0.01). The spiron treatment could decrease the blood levels of the AngII, Ald/ NO3-,ET/NO3-, AngII / NO3- and the tissue activities of the cardiac,lung, spleen, brain and liver CaN, but could increase blood NO3- concentration. CONCLUSION The ratios of the Ald over NO3- and the ET over NO3- can be elevated by the peritoneal injection of aldosterone,and then activate the tissue CaNs of the rat heart, lung, spleen and brain. But the spiron can keep stable the active factors of the endothelial system and decrease the effect of the activation on the tissue CaN.

参考文献/References

［1］ 符民桂，唐朝枢. 钙调神经磷酸酶的测定［J］.中国动脉硬化杂志，2000，8:82-83.

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［3］ 常连庆，谢晓华，陈 雯，等. 螺内酯抗钙调神经磷酸酶依赖的肾性高血压大鼠心肌肥厚作用机制 ［J］. 中华心血管病杂志，2004，32（3）：254-257.

［4］ Sanjay R, Damon D, Steven K ，et al. Mineralocorticoid receptor antagonism in experimental atherosclerosis［J］. Circulation，2002, 105(18): 2212-2216.

备注/Memo

备注/Memo:
收稿日期：2004-04-26.基金项目： "十五"军队医药卫生科研基金重点课题资助（编号：02Z0010）
更新日期/Last Update: 2010-01-05