天津医药 ›› 2019, Vol. 47 ›› Issue (3): 245-249.doi: 10.11958/20182162

• 实验研究 • 上一篇    下一篇

内源性孤啡肽通过调节β1肾上腺素能受体对大鼠缺血性心律失常的影响

熊畅,韩毅 ,郭政   

  1. 1山西医科大学麻醉学系(邮编030001);2山西医科大学第二医院麻醉科
  • 收稿日期:2018-12-29 修回日期:2019-01-25 出版日期:2019-03-15 发布日期:2019-04-24
  • 通讯作者: 韩毅 E-mail:13753171979@163.com

The influence of endogenous nociceptin/orphanin FQ (N/OFQ) in ischemic arrhythmia by regulating β1-adrenergic receptor in rats

XIONG Chang,HAN Yi,GUO Zheng   

  1. 1 Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China;2 Department of Anesthesiology,the Second Hospital of Shanxi Medical University
  • Received:2018-12-29 Revised:2019-01-25 Published:2019-03-15 Online:2019-04-24

摘要: 目的 探讨内源性孤啡肽(N/OFQ)对大鼠缺血性心律失常的影响以及心肌细胞β1肾上腺素能受体(β1-AR)在其中的作用。方法 采用结扎左冠状动脉前降支(冠脉)的方法制备大鼠急性心肌缺血模型。将60只大鼠按随机数字表法分为3组,即假手术组(Sham组)、冠脉结扎组(CAO组)和孤啡肽受体拮抗剂(UFP-101)预处理组(U+CAO组),每组20只。3组大鼠分别在冠脉结扎后15 min和1 h 2个时间点各处死10只大鼠。记录心电数据,采用Western blot法分别检测心肌细胞膜以及全细胞β1-AR的表达,RT-qPCR法检测β1-AR mRNA的表达。结果 与Sham组比较,CAO组出现缺血性心律失常,且主要集中在冠脉结扎后15 min内,UFP-101预处理显著降低心律失常发生。15 min 时:与 Sham 组比较,CAO 组全细胞 β1-AR、β1-AR mRNA 表达下调,而细胞膜 β1-AR 上调(均 P<0.05),U+CAO组全细胞β1-AR蛋白及其mRNA表达无统计学意义(均P>0.05),而细胞膜β1-AR下调(P<0.05);与CAO组比较,U+CAO组全细胞β1-AR蛋白及mRNA表达上调,而细胞膜β1-AR下调(P<0.05)。1 h时:与Sham组比较,CAO组和U+CAO组全细胞β1-AR蛋白及mRNA表达上调,而细胞膜β1-AR下调(均P<0.05)。结论 内源性N/OFQ可上调心肌细胞膜β1-AR参与大鼠缺血性心律失常过程。

关键词: 心律失常, 心性, 心肌缺血, 受体, 肾上腺素能β1, 孤啡肽

Abstract: Objective To investigate the effect of nociceptin/orphanin FQ (N/OFQ) on ventricular arrhythmias induced by acute myocardial ischemia, and the role of β1-adrenergic receptor (β1-AR) thereof. Methods The rat model of acute myocardial ischemia was prepared by ligating the left anterior descending branch of the coronary artery. A total of 60 rats were randomly divided into 3 groups, namely sham-operation group (Sham group), coronary artery occlusion group (CAO group) and the pretreatment of N/OFQ receptor antagonist (UFP-101) group (U+CAO group). Ten rats were sacrificed at 15 minutes, and another ten rats were sacrificed at 1 hour after CAO. Electrocardiographic data were recorded. The expressions of β1-AR from myocardial cell membrane and whole cell were detected by Western blot assay. The expression of β1-AR mRNA was detected by RT-qPCR. Results Compared with Sham group, ischemic arrhythmias occurred in CAO group, and mainly occurred during 15 minutes after CAO. The pretreatment with UFP-101 can significantly decrease ischemic arrhythmias. At 15 min, compared with Sham group, the expressions of β1-AR and β1-AR mRNA in whole cell were downregulated, and the membrane β1-AR was up-regulated (all P<0.05) in CAO group. Meanwhile, no significant differences were found in the expression of β1-AR and its mRNA in whole cell (all P>0.05). The expression of membrane β1-AR was down-regulated (P<0.05) in U+CAO group. Compared with the CAO group, the expressions of β1-AR and β1-AR mRNA in whole cell were up-regulated while the β1-AR in membrane was down-regulated (all P<0.05) in U+CAO group. At 1 h,compared with Sham group, the expressions of β1-AR and β1-AR mRNA in the whole cell were up-regulated, and the membrane β1-AR was down-regulated (all P<0.05) in CAO and U+CAO group. Conclusion Endogenous N/OFQ can regulate the expression of β1-AR in myocardial cell membrane and participate in the process of ischemic arrhythmia in rats.

Key words: arrhythmias, cardiac, myocardial ischemia, receptors, adrenergic, beta-1, nociceptin/orphanin FQ