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在大鼠离体心脏缺血/再灌注后,毒蕈碱型乙酰胆碱受体-2、4 和 α7-烟碱型乙酰胆碱受体表达的改变。

Alterations of muscarinic acetylcholine receptors-2, 4 and α7-nicotinic acetylcholine receptor expression after ischaemia / reperfusion in the rat isolated heart.

机构信息

Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, China.

出版信息

Clin Exp Pharmacol Physiol. 2010 Dec;37(12):1114-9. doi: 10.1111/j.1440-1681.2010.05448.x.

Abstract
  1. Cardiac acetylcholine receptors are involved in the negative inotropic effect of the vagus and the protection of the stimulated vagal nerve against myocardial ischaemic injury. Acetylcholine receptors consist of five types of muscarinic acetylcholine receptors (M AChR) and several nicotinic acetylcholine receptors (nAChR). Notably, ischaemic heart disease is accompanied by substantial withdrawal of vagal activity. However, it is not entirely clear what the changes of M(2,4) AChR and α7-nAChR expression are after cardiac ischaemia/reperfusion (I/R) injury. 2. Cardiac functions were continuously recorded in Langendorff mode during 30 min of ischaemia and 60 min of reperfusion. Lactate dehydrogenase (LDH) leakage was measured. M(2,4) AChRs and α7-nAChR expression were measured by reverse transcription polymerase chain reaction and western blot. 3. In hearts exposed to I/R injury, left ventricular development pressure, heart rate and ± dP/dt decreased significantly compared with the controls. LDH leakage increased with respect to the controls during reperfusion. 4. In normal hearts, expression of M(2,4) AChR in the left ventricle were lower than in atria and the right ventricle, whereas expression of α7-nAChR was dramatically higher in the left ventricle and right ventricle than the atria. After reperfusion, the mRNA and protein expression of M(2) AChR increased notably in the left and right ventricle, and α7-nAChR was enhanced significantly in the left ventricle. M(4) AChR mRNA expression reduced notably after ischaemia and recovered to the control level after reperfusion in the atria, but the protein level did not change. 5. In conclusion, the increase in M(2) AChR and α7-nAChR after reperfusion might be the compensatory response to myocardial I/R injury, providing new information for treatment of myocardial I/R injury.
摘要
  1. 心脏乙酰胆碱受体参与迷走神经的负性变力作用和刺激迷走神经防止心肌缺血性损伤。乙酰胆碱受体由五种类型的毒蕈碱乙酰胆碱受体(M AChR)和几种烟碱型乙酰胆碱受体(nAChR)组成。值得注意的是,缺血性心脏病伴随着迷走神经活动的大量撤出。然而,心脏缺血/再灌注(I/R)损伤后 M(2,4) AChR 和 α7-nAChR 表达的变化尚不完全清楚。

  2. 在缺血 30 分钟和再灌注 60 分钟期间,连续在 Langendorff 模式下记录心脏功能。测量乳酸脱氢酶(LDH)漏出量。通过逆转录聚合酶链反应和 Western blot 测量 M(2,4) AChR 和 α7-nAChR 的表达。

  3. 在 I/R 损伤的心脏中,与对照组相比,左心室发展压、心率和± dP/dt 明显降低。与对照组相比,再灌注期间 LDH 漏出量增加。

  4. 在正常心脏中,左心室 M(2,4) AChR 的表达低于心房和右心室,而α7-nAChR 在左心室和右心室的表达明显高于心房。再灌注后,左、右心室 M(2) AChR 的 mRNA 和蛋白表达显著增加,左心室 α7-nAChR 显著增强。缺血后 M(4) AChR mRNA 表达明显减少,再灌注后恢复至对照组水平,但蛋白水平不变。

  5. 综上所述,再灌注后 M(2) AChR 和 α7-nAChR 的增加可能是心肌 I/R 损伤的代偿反应,为心肌 I/R 损伤的治疗提供了新的信息。

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