国际麻醉学与复苏杂志   2017, Issue (1): 4-4
    
右美托咪定致家兔窦性心动过缓模型中窦房结去甲肾上腺素、乙酰胆碱、毒蕈碱受体2及腺苷受体1的变化
钟毅, 殷永强, 祝瑜, 田磊1()
1.贵阳医学院附属医院
The expression changes of norepinephrine, acetylcholine, muscarinic receptors-2, adenosine receptors-1 on sinus bradycardia model caused by dexmedetomidine in rabbits
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摘要：

目的　 研究右美托咪定（dexmedetomidine, Dex）致家兔窦性心动过缓模型心脏窦房结中去甲肾上腺素（norepinephrine, NE）、乙酰胆碱（acetylcholine, Ach）、毒蕈碱受体2（muscarinic receptors 2, M2）及腺苷受体1（adenosine receptors 1, A1）的变化，探讨其致心动过缓的机制。　方法　健康新西兰大白兔24只按随机数字表法分为3组（每组8只）：对照组（C组）、低剂量Dex组（D1组）和高剂量Dex组（D2组）。C组通过耳缘静脉持续泵注生理盐水；D1组Dex负荷量10 μg/kg泵注10 min，持续泵注量5 μg·kg-1·h-1泵注50 min；D2组Dex负荷量60 μg/kg泵注10 min，持续泵注量30 μg·kg-1·h-1泵注50 min。戊巴比妥钠基础麻醉后，迅速建立BP和ECG监测，3组实验过程中均于Dex注射前（T0）及Dex注射后15 min（T1）、30 min（T2）、60 min（T3）监测HR和MAP，Dex泵注结束后迅速开胸取出心脏，准确分离家窦房结组织，采用实时荧光定量法、免疫组化法、双抗体夹心法检测组织中NE、Ach、M2、A1。　结果　T0 时点3组MAP、HR的基础值比较，差异无统计学意义（P>0.05），T1、T2、T3时点D1组、D2组的MAP、HR均较C组低（P<0.05），T1、T2、T3时点D2组的HR均较D1组低（P<0.05）。M2基因相对表达量3组间比较，差异无统计学意义（P>0.05），A1基因相对表达量D2组比C组［（13±5）比（5±3）］、D1组［（13±5）比（6±4）］显著增加（P<0.05）；M2、A1蛋白平均光密度变化均为D2组比C组［（0.240±0.040）比（0.193±0.022），（0.290±0.043）比（0.185±0.017）］、D1组［（0.240±0.040）比（0.194±0.031），（0.290±0.043）比（0.202±0.022）］显著增加（P<0.05）。D1组、D2组NE比C组显著降低（P<0.05），D1组与D2组NE比较，差异无统计学意义（P>0.05）；D2组的Ach比C组、D1组显著增高（P<0.05）。　结论　Dex使交感神经递质NE降低，迷走神经递质Ach仅在大剂量组显著增加，大剂量Dex直接兴奋迷走神经，M2、A1的变化在大剂量组呈显著上调趋势。
关键词： 右美托咪定；　窦性心动过缓；　窦房结；　去甲肾上腺素；　乙酰胆碱；　毒蕈碱受体2
Abstract:

Ｏｂｊｅｃｔｉｖｅ　To investigate the effects of dexmedetomidine(Dex) on norepinephrine(NE), acetylcholine(Ach), muscarinic receptors 2(M2), adenosine receptors 1(A1) of rabbits，and to clarify the mechanism of dex-induced bradyarrhythmias.　Methods　Twenty four healthy male rabbits were randomly divided into 3 groups(n=8), including control(group C), low dose of Dex (group D1), and high dose of Dex(group D2). Rabbits were administered normal saline in group C. Rats in group D1 were administered Dex at loading dose of 10 μg/kg for 10 min, and then at 5 μg·kg-1·h-1 for 50 min. Rats in group D2 were administered with Dex at loading dose of 60 μg/kg for 10 min and then at 30 μg·kg-1·h-1 for 50 min. After rabbits were anesthesia by sodium pentobarbital, basic operations were quickly were completed in order to measure MAP and ECG. HR, MAP were obtained before(T0), 15 min after (T1), 30 min after(T2), 60 min after(T3) intravenous pumping of Dex. After observation of Dex pump injection, hearts were quickly removed and divided accurately the sinus node. The experiment indicators were detected by the Real-time quantitative PCR, Immunohistochemical, ELISA.　Results　There was no significant difference in HR and MAP at T0 among the three groups(P>0.05). Compared with group C, HR, MAP were decreased at T1, T2, T3 in group D1, D2(P<0.05), HR of group D2 were decreased than group D1 at T1, T2, T3(P<0.05). There was no significant difference relative gene expression of M2 among the three groups (P>0.05). Relative gene expression of A1 in group D2 significantly increased than group C[(13±5) vs (5±3)], D1[(13±5) vs (6±4)](P<0.05). Protein mean Optical density of M2, A1 in group D2 significantly increased than group C[(0.240±0.040) vs (0.193±0.022), (0.290±0.043) vs (0.185±0.017)], group D1[(0.240±0.040) vs (0.194±0.031), (0.290±0.043) vs (0.202±0.022)](P<0.05). NE in group D1, D2 were significantly decreased than group C(P<0.05), there were no significant difference between group D1 and D2(P>0.05). Ach in group D2 were significantly increased than group C, D1(P<0.05).　Conclusions　Dex decreases NE of sympathetic transmitter and Ach vagus nerve neurotransmitter of only increases significantly in the high-dose group. High dose of Dex directly increasing vagus nerve activities. M2, A1 in the high-dose group showed a trend of rise significantly.
Key words: Dexmedetomidine;　Sinus bradycardia;　Sinuatrial node;　Norepinephrine;　Acetylcholine;　Muscarinic receptors-2;　Adenosine receptors-1;　Rabbits