外源性醛固酮调控大鼠心肌钙调神经磷酸酶的研究  

The external aldosterone regulating on the rat cardiac calcineurin

作　　者：谢晓华[1] 常连庆[1] 陈雯[1] 宋立功[1] 刘宁 张颖[1] 孙愚[1] 唐朝枢[3] 

机构地区：[1]解放军总医院 [2]解放军第272医院 [3]北京大学医学部

出　　处：《解放军医学杂志》2004年第9期798-800,共3页Medical Journal of Chinese People's Liberation Army

基　　金："十五"军队医药卫生科研基金重点资助课题 (编号 0 2Z0 0 1 0 )

摘　　要：目的　研究外源性醛固酮诱导的心肌内肥大信号分子———钙调神经磷酸酶(CaN)活性和分布变化及其调控机制。方法　取雄性Wistar大白鼠 2 1只 ,随机分为 3组 ,醛固酮 (Ald)组 (以Ald 1 8μg/d腹腔内注射 4周 )、螺内酯组 (以Ald处理同时予螺内酯2 0mg·kg-1 ·d-1 灌胃 4周)及正常对照组。以放免法测血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肌组织CaN活性 ;以免疫组化法观察CaNAβ抗原在心肌细胞内的分布。结果　Ald组大鼠血Ald浓度较对照组上升了 1 6 2倍 ;血NO-3 浓度明显下降 ;而Ald /NO-3 上升了 2 95倍 ,心肌组织CaN活性升高了 1 4 7倍 ;CaNAβ抗原分布于细胞浆 ,在近胞膜处及细胞核周CaNAβ染色加深。螺内酯干预使血AngⅡ浓度下降、NO-3 浓度明显升高 ;Ald/NO-3 、ET/NO-3 、AngⅡ/NO-3 和心肌组织CaN活性均明显下降 ;近胞膜处及细胞核周CaNAβ染色减轻。结论　醛固酮可能是内皮活性物质稳态失衡及心肌细胞内信号分子 CaN激活的重要刺激因子。目的　研究外源性醛固酮诱导的心肌内肥大信号分子———钙调神经磷酸酶(CaN)活性和分布变化及其调控机制。方法　取雄性Wistar大白鼠 2 1只 ,随机分为 3组 ,醛固酮 (Ald)组 (以Ald 1Objective To investigate the changes of the activity and the distribution of the rat cardiac calcineurin (CaN) which is the signalling molecule of the hypertrophy induced by the external aldosterone(Ald), and to detect the mechanism of the regulation of CaN. Methods 21 male wister rats were randomly divided into 3 groups: group Ald(7 rats), treated with Ald 18μg/d, peritoneal injection (i p) for 4 weeks; group spironolactone (spiron) (7 rats), treated with Ald and with spiron 20mg·kg -1 ·d -1 oral for 4 weeks; and group control (7 rats). The plasma concentrations of Ald, angiotensin Ⅱ(Ang Ⅱ)and endothelin(ET), blood levels of NO, the tissue activity of the CaN and distribution of CaN Aβ in the myocardium of the left ventricle, were detected in the rats by the radioimmunoassay , by the nitrate assay, by the chromophoric assay and by the immunohistochemistry, respectively. Results The concentration of the plasma Ald increased by 1 62 times, the blood NO - 3 concentration was deceased, the ratio of Ald over NO - 3( Ald/ NO - 3) increased by 2 95 times, and the cardiac tissue levels of CaN activity was were 1 47 times higher, in the rats treated with ald than in the normotensive rats. CaN Aβ distributed over cardiac cytoplasm, and the positive dyeing of the local CaN Aβ in the cytoplasm was thick near the cell membrane in the rats treated with Ald. The treatment with spiron could decreased the blood levels of the AngII?Ald/ NO - 3?ET/NO - 3?AngII/ NO - 3 and the tissue activity of myocardial CaN, positive dyeing of the local CaN Aβ in the cytoplasm, and increased blood NO - 3 concentration. Conclusion The aldosterone may be the main stimuli factor which can damage the balance of the blood active factors, and then make a novel cardiac hypertrophic signalling molecule calcineurin activated and redistributed in the cytoplasm of the rat left ventricular myocardium

关 键 词：醛固酮 钙调神经磷酸酶 一氧化氮 内皮素 螺内酯 

分 类 号：R541.3[医药卫生—心血管疾病]