高血压大鼠心肌肾素-血管紧张素系统的日变化

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (8): 863-867.

高血压大鼠心肌肾素-血管紧张素系统的日变化

黄建寨, 魏立, 王晓军, 李庆平

南京医科大学药理学系, 南京 210029, 江苏

收稿日期:2006-03-22 修回日期:2006-05-20 出版日期:2006-08-26 发布日期:2020-11-05
作者简介:黄建寨, 男, 硕士研究生, 研究方向:心血管药理学。
基金资助:
国家自然科学基金资助项目(No30271506)

Enhanced diurnal variations of cardiac renin-angiotensin system in hypertensive rats

HUANG Jian-zhai, WEI Li, WANG Xiao-jun, LI Qing-ping

Department of Pharmacology , Nanjing Medical University, Nanjing 210029 , Jiangsu, China

Received:2006-03-22 Revised:2006-05-20 Online:2006-08-26 Published:2020-11-05

摘要/Abstract

摘要： 目的探讨高血压大鼠心肌肾素-血管紧张素系统(RAS) 元件基因(ATNG 、AT1R 、AT2R) 的昼夜节律表达与高血压左心室肥厚的相关性。方法建立肾性高血压大鼠的模型。取自发性高血压大鼠(SHR) , 肾性高血压大鼠(RHR) 以及正常SD 大鼠,在12 h 光暗交替的环境中饲养2 周后, 每隔4 h 取心脏, 测心重指数等各项指标, 用RT-PCR 的方法检测高血压大鼠心肌组织与正常大鼠心肌组织中血管紧张素原(ATNG) , 血管紧张素Ⅱ受体1 型(AT1 R) 与血管紧张素Ⅱ受体2 型(AT2R) 表达的变化。结果 SHR 和RHR 的左心重与全心重比值及全心重与体重比值较对照组明显增大;SHR 和RHR 组心脏RAS元件基因表达较对照组增高。RAS 元件基因的mRNA的表达都表现出昼夜节律, SHR 和RHR 组昼夜变化的幅度较对照组明显。结论 RAS 元件基因的过表达和其波动的增加在心肌肥厚的发病过程中可能起到了一定的作用。

关键词: 心肌肥厚, 肾素-血管紧张素系统, 昼夜节律

Abstract: AIM: To investigate whether the circadian mRNA expression of the renin-angiotensin system (RAS) components (ATNG 、AT1R、AT2R) in myocardium is correlated with left ventricular hypertrophy in both spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR).METHODS: The model of RHR as established using 2K1C (two-kidney one clip).SHR, RHR, and normotensive control rats (CON) were oused in a separate environment-controlled room for two eeks, in which a strict 12-hour light 12-hour dark cycle egimen was enforced (lights on at 9 ∶00, zeitgeber time ZT0]).Rats were killed every 4 hours from 9 ∶00 am ZT0) to 5 ∶00 pm (ZT20) on three separate days.We xamined the circadian mRNA expression of ATNG 、AT1 R、AT2R in the hearts of SHR, RHR and CON rats by T-PCR.RESULTS: Heart weight to body weight ratios nd left ventricle weight to heart weight ratios indicated a ignificant increase in SHR and RHR compared with normotensive ats.The cardiac mRNA expression of the RAS omponents showed circadian oscillations in SHR, RHR nd CON rats.The amplitudes of these circadian fluctuations ere greater in the SHR and RHR than in the CON ats.The mRNA levels of the RAS components were increased n the SHR and RHR compared with the CON rats t many time points.CONCLUSION: The data indicate hat overexpression and enhanced amplitudes of circadian luctuations of RAS components in SHR and RHR may ay a role in the development of left ventricular hypertrophy.

Key words: hypertrophic myocardium, renin-angiotensin ystem, circadian rhythm

中图分类号:

R965.2
R966

黄建寨, 魏立, 王晓军, 李庆平. 高血压大鼠心肌肾素-血管紧张素系统的日变化[J]. 中国临床药理学与治疗学, 2006, 11(8): 863-867.

HUANG Jian-zhai, WEI Li, WANG Xiao-jun, LI Qing-ping. Enhanced diurnal variations of cardiac renin-angiotensin system in hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(8): 863-867.

参考文献

1 Hannan R, Jenkins A, Brandenburger Y.Cardiac hypertrophy:a matter of translation[J].Clin ExPPharmacol Physiol, 2003;30:517-27
2 JurkovicováD, DobesováZ, Kunes J, KrizanováO.Different xpression of renin-angiotensin system components in hearts of ormotensive and hypertensive rats[J].Physiol Res, 2001;50:35-42
3 Makino N, Sugano M, Otsuka S, Hata T.Molecular mechanism f angiotensin II type I and type II receptors in cardiac hypertrophy f spontaneously hypertensive rats[J].Hypertension, 1997;30:796-802
4 Guo YF, Stein PK.Circadian rhythm in the cardiovascular system chronocardiology[J].Am Heart J, 2003;145:779-86
5 Reppert SM, Weaver DR.Molecular analysis of mammalian circadian hythms[J].Annu Rev Physiol, 2001;63:647-76
6 黄新艳, 魏立, 李晓林, 朱东亚, 李庆平.血管紧张素Ⅱ对乳大鼠心肌细胞时钟基因表达的影响[J].中国药理学与毒理学, 2005;19:194-8
7 Fujii N, Tanaka M, Ohnishi J, Yukawa K, Takimoto E, Shimada, et al.Alterations of angiotensin II receptor contents in ypertrophied hearts [J].Biochem Biophys Res Commun,1995;212:326-33
8 Senbonmatsu T, Ichihara S, Price EJ, Gaffney FA, Inagami T.Evidence for angiotensin II type 2 receptor-mediated cardiacmyocyte enlargement during in vivo pressure overload[J].J ClinInvest, 2000;106:R25-9
9 Ichihara S, Senbonmatsu T, Price EJ, Ichiki T, Gaffney FA,Inagami T.Angiotensin II type 2 receptor is essential for left entricular hypertrophy and cardiac fibrosis in chronic angiotensin I-induced hypertension[J].Circulation, 2001;104:346-51
10 Akishita M, Iwai M, Wu L, Zhang L, Ouchi Y, Dzau VJ,Horiuchi M.Inhibitory effect of angiotensin II type 2 receptor on
11 coronary arterial remodeling after aortic banding in mice[J].coronary arterial remodeling after aortic banding in mice[J].Circulation, 2000;102:1684-9
12 Beverly L, Metcalfe, Matthew J, Huentelman, Leonard D.Prevention of Cardiac Hypertrophy by Angiotensin II Type-2 Receptor Gene[J].Transfer Hypertension, 2004;43:1233-8
13 Portman MA.Molecular clock mechanisms and circadian rhythms intrinsic to the heart[J].Circ Res, 2001;89:1084-6
14 李晓林, 丁延魁, 黄新艳, 魏立, 朱东亚, 李庆平.高血压大鼠肥厚心肌中BMAL1 蛋白表达的研究[J].中国药理学通报, 2005;21:811-5

[1]	吴伟, 邓丽影. 昼夜节律失调性睡眠觉醒障碍的治疗策略#br#[J]. 中国临床药理学与治疗学, 2021, 26(5): 511-515.
[2]	李佳怡, 张益梦, 王晨曦, 李军, 潘燕. 昼夜节律睡眠-觉醒障碍与恶性肿瘤发生发展的关系[J]. 中国临床药理学与治疗学, 2021, 26(1): 76-81.
[3]	崔海鞠, 马张庆, 杨魁, 汪五三, 许慧芳, 栾家杰. 褪黑素在非杓型自发性高血压大鼠体内的时辰药动学研究[J]. 中国临床药理学与治疗学, 2020, 25(12): 1337-1343.
[4]	陈丹，郭玉金，杨梦琦，蔡骅琳，江沛. 血管紧张素(1-7)的神经活性研究进展[J]. 中国临床药理学与治疗学, 2018, 23(12): 1425-1430.
[5]	李忠洪，王平，周四桂，王桂香. 二甲双胍通过上调谷胱甘肽-S-转移酶μ₂抑制大鼠心肌肥厚[J]. 中国临床药理学与治疗学, 2017, 22(12): 1326-1331.
[6]	王政，汪和贵. A型激酶锚定蛋白介导的心肌肥厚调控机制的研究进展[J]. 中国临床药理学与治疗学, 2017, 22(11): 1304-1308.
[7]	张莹，王安才，王新，王德国，邢文. 阿托伐他汀对腹主动脉缩窄性高血压大鼠心肌组织蛋白酶S、K的影响[J]. 中国临床药理学与治疗学, 2016, 21(9): 968-972.
[8]	周四桂, 徐立朋, 路遥, 袁茜, 潘雪刁, 臧林泉. 非诺贝特通过上调短链酰基辅酶A脱氢酶抑制大鼠心肌肥厚[J]. 中国临床药理学与治疗学, 2013, 18(8): 868-873.
[9]	孙晓蕾, 管军, 于忠祥, 王少华, 闫美兴, 刘华强. 不同时间服用比索洛尔治疗非杓型原发性高血压的疗效评价[J]. 中国临床药理学与治疗学, 2011, 16(3): 292-296.
[10]	王燕, 张明升, 刘宇, 陈敏. 奈比洛尔对自发性高血压大鼠循环和主动脉肾素-血管紧张素系统的影响[J]. 中国临床药理学与治疗学, 2010, 15(7): 770-774.
[11]	冯瑞儿, 郑琳颖, 吕俊华, 潘竞锵, 肖柳英. 白芍总苷对代谢综合征-高血压大鼠改善胰岛素敏感性、降压和抗氧化作用[J]. 中国临床药理学与治疗学, 2010, 15(2): 154-159.
[12]	曹锦秀, 张丽萍, 高春林, 贾俊亚. 高血压与肾脏疾病中肾脏局部肾素-血管紧张素系统的激活及病理生理作用[J]. 中国临床药理学与治疗学, 2009, 14(12): 1436-1440.
[13]	韩军, 宋建国. 中药方剂鸡鸣散的时间药理学实验研究[J]. 中国临床药理学与治疗学, 2008, 13(7): 782-785.
[14]	黄文礼, 唐敏, 樊莹. 褪黑激素在人视网膜中的作用机制[J]. 中国临床药理学与治疗学, 2007, 12(7): 735-738.
[15]	胡群力, 梁群, 蔡其云. 缬沙坦干预非杓型高血压者恢复杓型血压昼夜节律后对血醛固酮水平的影响[J]. 中国临床药理学与治疗学, 2007, 12(1): 116-118.