β1 肾上腺素能受体反义寡核苷酸对肾性高血压大鼠血流动力学及心肌肥厚的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (9): 997-1001.

β₁ 肾上腺素能受体反义寡核苷酸对肾性高血压大鼠血流动力学及心肌肥厚的影响

严玲, 王晋明, 王芳, 梁远红, 夏芳, 宋晓华

武汉大学人民医院心内科, 武汉430060, 湖北

收稿日期:2004-06-23 修回日期:2004-07-29 出版日期:2004-09-26 发布日期:2020-11-23
通讯作者: 王晋明, 男, 教授, 博士生导师, 研究方向:高血压病防治。Tel:027-88041911-2213
作者简介:严玲, 女, 硕士研究生, 研究方向:高血压病防治。Tel:13545126835 E-mail:doctoryl@126. com

Effects of β₁-adrenergic receptor mRNA antisense oligodeoxynucleotide on the hemodynamics and cardiac hypertrophy in renal hypertensive rats

YAN Ling, WANG Jin-Ming, WANG Fang, LIANG Yuan-Hong, XIA Fang, SONG Xiao-Hua

Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei, China

Received:2004-06-23 Revised:2004-07-29 Online:2004-09-26 Published:2020-11-23

摘要/Abstract

摘要： 目的: 观察阳离子脂质体(DOTAP DOPE) 介导的β₁ 肾上腺素能受体mRNA 反义寡核苷酸(β₁-AS-ODN) 对肾性高血压大鼠血流动力学及心肌肥厚的影响。方法: 建立二肾一夹(2K1C) 肾性高血压大鼠模型, 随机分为假手术组、模型组、反向寡核苷酸组、反义寡核苷酸组和卡维地洛(carvedilol) 组。ODN与DOTAP/DOPE 以1:2 摩尔比混合, 4 周末尾静脉注射0. 5 mg·kg^-1, 卡维地洛10 mg·kg^-1·d^-1 灌胃4周。定期测血压, 8 周末测血流动力学参数, 左室重量指数(LVWI) 及血浆内皮素-1 (ET-1) 浓度, 并对LVWI 与ET-1 进行线性相关分析。结果: 与反向寡核苷酸组比, β₁-AS-ODN 能降低血压最高达39 mmHg 并持续27 d(30. 44±6. 50, P<0.01), 降低左室收缩压(LVSP) (P<0. 05) 、左室舒张末压(LVEDP) (P<0.01), 升高左室最大收缩和舒张速率(±dp d tmax) (P<0.01), 降低LVWI(P<0. 05) 及血浆ET-1(P<0.01); 与卡维地洛组比, 各指标均无显著性差异。LVWI 与ET-1 显著正相关(r =0. 749, P<0.01) 。结论: DOTAP DOPE 介导的β₁-AS-ODN 单剂量静脉注射能持续降压, 改善血流动力学, 预防心肌肥厚, 可能与其降低血浆ET-1 有关。

关键词: β₁ 肾上腺素能受体, 反义寡核苷酸, 肾性高血压, 血流动力学, 心肌肥厚

Abstract: AIM: To investigate the effects of β₁-adrenergic receptor mRNA antisense oligodeoxynucleotide (β₁-AS-ODN) mediated by the cationic liposomes (DOT-AP/DOPE) on the hemodynamics and cardiac hypertrophy of renal hypertensive rats.METHODS: The two-kidney and one-clip (2K1C) rat models were established and divided into five groups: the sham-operated group, the 2K1C group, the 2K1C +inverted ODN (IN-ODN ) group, the 2K1C + antisense oligodeoxynucleotide (ASODN) group and the 2K1C +carvedilol group. Single intravenous injection of ODN 0. 5 mg·kg^-1 was given after four weeks of operation and carvedilol 10 mg·kg^-1 ·d^-1 was administrated for 4 weeks. Blood pressure was measured regularly. Hemodynamic parameters, left ventricular weight index (LVWI) and plasma endothelin-1(ET-1) concentration were measured after eight weeks of operation The linear correlation between LVWI and ET-1 were analyzed.RESULTS: Compared with the IN-ODN group, β₁-AS-ODN significantly decreased SBP (P<0.01), increased±d_p dt_max (P<0.01), and had an obvious suppressive effect on LVSP (P<0. 05 ), LVEDP (P<0.01), LVWI (P<0. 05) and ET-1(P<0.01). No significant difference was found between the AS-ODN group and the carvedilol group. In addition, LVWI positively correlated with ET-1 (r =0.749, P<0.01).CONCLUSION: β₁-AS-ODN mediated by the cationic liposomes has an effective long-term antihypertensive effect with single intravenous injection. It can also improve the hemodynamics and attenuate cardiac hypertrophy. These effects may relate to their effect of decreasing the concentration of plasma ET-1.

Key words: beta-1 adrenergic receptor, antisense oligodeoxynucleotide, renal hypertension, hemodynamics, cardiac hypertrophy

中图分类号:

R541.3

严玲, 王晋明, 王芳, 梁远红, 夏芳, 宋晓华. β₁ 肾上腺素能受体反义寡核苷酸对肾性高血压大鼠血流动力学及心肌肥厚的影响[J]. 中国临床药理学与治疗学, 2004, 9(9): 997-1001.

YAN Ling, WANG Jin-Ming, WANG Fang, LIANG Yuan-Hong, XIA Fang, SONG Xiao-Hua. Effects of β₁-adrenergic receptor mRNA antisense oligodeoxynucleotide on the hemodynamics and cardiac hypertrophy in renal hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(9): 997-1001.

参考文献

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β₁ 肾上腺素能受体反义寡核苷酸对肾性高血压大鼠血流动力学及心肌肥厚的影响

Effects of β₁-adrenergic receptor mRNA antisense oligodeoxynucleotide on the hemodynamics and cardiac hypertrophy in renal hypertensive rats

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