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慢性间歇性低压低氧对心肌α 1 受体的影响参与大鼠心脏保护

王莹萍^1,2, 崔芳², 张利萍², 杨长瑛², 关玥², 周兆年², 张翼^2,*

¹ 河北医科大学生理学教研室，石家庄 050017；²中国科学院上海生命科学研究院，上海 200031

摘要

本研究通过肌肉收缩描记方法，应用α1 肾上腺素能受体激动剂——苯肾上腺素(phenylephrine, PE)和α1 受体阻断剂 ——哌唑嗪(prazosin, PRA)探讨慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia, CIHH)大鼠心室乳头状肌α1 受体的变 化以及α1 受体在心脏保护中的作用。雄性Sprague-Dawley 大鼠66 只，随机分为4 组：对照组(control, Con)、CIHH 处理14 天组(CIHH14)、CIHH 处理28 天组(CIHH28)和CIHH 处理42 天组(CIHH42)。CIHH 处理动物置于低压氧舱内，分别接受14、28、42 天相当于5 000 m 高原(pB=404 mmHg, pO2=84 mmHg)低氧处理，每天6 h。对照组动物除不接受低氧处理外，其余条 件同CIHH 处理动物。大鼠以戊巴比妥钠(3.0~3.5 mL/kg 体重)腹腔注射麻醉后立即取出心脏，分离右室乳头状肌，用氧饱和 的改良台氏液恒温(37 ºC)、恒速(12 mL/min)灌流，电刺激诱发乳头状肌收缩。通过累加给药法，观察不同浓度(1×10-7、1×10-6 和1×10-5 mol/L) PE 对大鼠乳头状肌收缩的影响；用模拟缺血液以及加入PRA (1×10-6 mol/L)的模拟缺血液灌流，观察各组乳 头状肌收缩的变化。结果如下：(1) PE 增加各组乳头状肌的最大收缩力(maximal isometric tension, Pmax)和最大张力上升速率 (maximal velocity of tension development, PdT/dt)，作用呈剂量依赖性(P<0.05)；CIHH28、CIHH42 处理组乳头状肌对PE 反应性 增强(P<0.05)。最大浓度PE (1×10-5 mol/L)作用下，CIHH28 组的Pmax 和PdT/dt 分别较基础值增加51.2% 和44.5%，CIHH42 组 的Pmax 和PdT/dt 分别增加48.6% 和44.5%，较对照组(28.7% 和24.5%)明显增加(P<0.05)；(2) CIHH 处理可以对抗模拟缺血液对 乳头状肌收缩的抑制。CIHH28 和CIHH42 组的Pmax 和PdT/dt 降低幅度分别为59.6%，53.6% 和60.4%，49.9%，明显小于对照 组(74.4%，64.7%) (P<0.05)；(3) α1 受体阻断剂PRA (1×10-6 mol/L)可取消CIHH 对抗缺血的保护作用。以上结果表明，CIHH 处理增强大鼠心肌α1 肾上腺素能受体活动，此作用可能是CIHH 处理对抗心肌缺血/ 再灌注损伤的机制之一。

关键词： 慢性间歇性低压低氧; α 1 肾上腺素能受体; 苯肾上腺素; 哌唑嗪; 乳头状肌; 大鼠

分类号：Q494

Effect of chronic intermittent hypobaric hypoxia on α1-adrenergic receptor of myocardium participates in the cardioprotection

WANG Ying-Ping^1,2, CUI Fang², ZHANG Li-Ping², YANG Chang-Ying², GUAN Yue², ZHOU Zhao-Nian², ZHANG Yi^2,*

¹Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China；² Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Abstract

The purpose of the present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on α1- adrenergic receptors and the role of α1-adrenergic receptors in the protection of CIHH against ischemic injury of myocardium. Sixtysix adult male Sprague-Dawley rats were randomly divided into four groups: control group (Con), 14-day CIHH treatment group (CIHH14), 28-day CIHH treatment group (CIHH28) and 42-day CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia mimicking 5 000 m altitude (pB=404 mmHg, pO2=84 mmHg) in a hypobaric chamber, 6 h daily for 14, 28 and 42 d, respectively. Control animals lived in the same environment as CIHH animals except hypoxia exposure. After anesthesia with sodium pentobarbital (3.0-3.5 mL/kg body weight, i.p.), papillary muscle was taken from the right ventricle of rat and perfused with modified Tyrode’s solution continuously, at constant temperature (37 ºC) and perfusion speed (12 mL/min). Muscle contraction was evoked by electric stimuli. Different concentrations (1×10-7, 1×10-6 and 1×10-5 mol/L) of phenylephrine (PE), an α1-adrenergic receptor agonist, were applied cumulatively to investigate the effect of PE on the mechanic contraction of right ventricular papillary muscles of rats in Con, CIHH14, CIHH28 and CIHH42 groups. Also, prazosin (1×10-6 mol/L), an α1-adrenergic receptor antagonist, was used to investigate the role of α1-adrenergic receptor in the protective effect of CIHH on papillary muscle. The results showed: (1) PE increased the maximal isometric tension (Pmax) and maximal velocity of tension development (PdT/dt) of muscle contraction in a dose-dependent manner (P< 0.05), and the increase of the muscle contraction was much greater in CIHH28 and CIHH42 rats than that in Con rats (P<0.05). Under 1×10-5 mol/L of PE, the increases of Pmax and PdT/dt over the baseline were 51.2% and 44.5% in CIHH28 group, 48.6% and 44.5% in CIHH42 group, and 28.7% and 24.5% in Con group, respectively; (2) The contraction of papillary muscle decreased during simulated ischemia, but the decrease was slighter in CIHH rats than that in Con rats (P<0.05). The decreases in Pmax and PdT/dt were 59.6% and 53.6% in CIHH28 group, 60.4% and 49.9% in CIHH42 group, and 74.4% and 64.7% in Con group, respectively; (3) The protective effect of CIHH on ischemic papillary muscle was abolished by prazosin (1×10-6 mol/L). The results of the present study suggest that CIHH increases the activity of α1-adrenergic receptor, which is possibly one of the mechanisms for the cardioprotection of CIHH.

Key words: chronic intermittent hypobaric hypoxia; α1-adrenergic receptor; phenylephrine; prazosin; papillary muscle; rat

收稿日期：2008-07-08　　录用日期：2008-10-15

通讯作者：张翼　　E-mail: zhyhenry@hotmail.com

引用本文：

王莹萍, 崔芳, 张利萍, 杨长瑛, 关玥, 周兆年, 张翼. 慢性间歇性低压低氧对心肌α 1 受体的影响参与大鼠心脏保护[J]. 生理学报 2009; 61 (1): 21-26.

WANG Ying-Ping, CUI Fang, ZHANG Li-Ping, YANG Chang-Ying, GUAN Yue, ZHOU Zhao-Nian, ZHANG Yi. Effect of chronic intermittent hypobaric hypoxia on α1-adrenergic receptor of myocardium participates in the cardioprotection. Acta Physiol Sin 2009; 61 (1): 21-26 (in Chinese with English abstract).