| Objective:Early stage of acute myocardial ischemia can lead to severe ventricular arrhythmias,have a significant impact on the prognosis of patients,and can lead to sudden death.The pathological process of ischemic ventricular arrhythmias is carried out with the participation of various factors,in which the excessive increase of cardiac sensory and sympathetic activation plays an important role.In previous studies,we found that in the early stage of acute myocardial ischemia,by antagonizing nociceptin/orphanin FQ receptors,it can reduce the occurrence of ischemic arrhythmia,but its specific mechanism is still unclear.The aim of this study was to investigate the relationship between endogenous nociceptin/orphanin FQ involvement in ischemic arrhythmia and cardiac sympathetic activity and norepinephrine transporter expression,and to provide experimental basis for further study of the mechanism of ischemic arrhythmia.Methods:The experimental animals were healthy adult male SD rats,aged from 6 to 7weeks,with a mass of 250 to 270 g.The rat model of acute myocardial ischemia was established by ligating the anterior descending branch of the left coronary artery.This experiment consists of three parts:Part one:Antagonistic effect of endogenous nociceptin/orphanin FQ on ventricular arrhythmia in early acute myocardial ischemia?15min?in ratsThe rats were divided into three groups:sham-operation group?Sham group?,coronary artery ligature group?CAO group?and the pretreatment of N/OFQ receptor antagonist?UFP-101?group?U+CAO group?.The sham group had open chest and subcoronary thread but no ligatio;The CAO group opened chest and ligated coronary artery;In the U+CAO group,UFP-101(1×10-9mol/L),a specific antagonist of OFQ,was injected into the caudal vein in a volume of 1ml/kg,at 10 min before coronary artery ligation,and the other two groups were injected with the same amount of normal saline via caudal vein.Ventricular arrhythmia data were recorded and analyzed from 10 min before operation to 15 min after myocardial ischemia.Part two:Antagonistic effects of endogenous nociceptin/orphanin FQ receptors on plasma norepinephrine Levels and heart rate variability in early acute myocardial ischemia?15min?in ratsHeart rate variability?HRV?from 10 min before operation to 15 min after myocardial ischemia was recorded and analyzed;After 15 min of myocardial ischemia,1ml blood was drawn from left ventricle by syringe,collected in the test tube containing K-EDTA,centrifuged to get the plasma,and the plasma sample was kept at-80?.Plasma samples were detected by enzyme-linked immunosorbent assay?ELISA?.Part three:Antagonistic effects of endogenous nociceptin/orphanin FQ receptors on the expression of norepinephrine transporter in early acute myocardial ischemia?15min?in ratsTotal protein and membrane protein expression of norepinephrine transporter in myocardial ischemia region of rats were detected by Western blot?western blot?after 15min of coronary artery ligationResults:1.The occurrence of ventricular arrhythmias within 15 minutes after acute myocardial ischemia in each groupSingle-ventricular ectopic beat?VEB?only occurred after subcoronary threading in the Sham group,but ventricular tachycardia?VT?and ventricular fibrillation?VF?did not occur.Compared with the Sham group,the VEB frequency,VT+VF frequency,VT+VF duration and arrhythmia score were increased in the CAO group?all p<0.05?,Compared with the Sham group,the VEB frequency increased in the U+CAO group,but there were no significant differences in VT+VF frequency,VT+VF duration and arrhythmia score?p>0.05?;Compared with the U+CAO group,the VT frequency,VT+VF frequency,VT+VF duration and arrhythmia score increased further in the CAO group?all p<0.05?.2.Comparison of plasma norepinephrine levels 15 min after acute myocardial ischemia in each groupCompared with the Sham group,the plasma norepinephrine level of both CAO and U+CAO groups was significantly higher?p<0.05?;Compared with the U+CAO group,the plasma norepinephrine level in the CAO group increased further,and the difference was statistically significant?p<0.05?.3.Comparison of heart rate variation in 15 min after acute myocardial ischemia in each groupThe SDNN?RMSSD?HF values of U+CAO group and CAO group decreased significantly compared with the Sham group?p<0.05?,but there was no significant difference between the two groups?p>0.05?;Compared with the Sham Group,the LF/HF Values of U+CAO group and CAO group were significantly higher?p<0.05?,and the LF/HF values of the CAO group were significantly higher than those of U+CAO group?p<0.05?.4.Expression of norepinephrine transporter 15 min after acute myocardial ischemia in ratsThere was no significant difference in total norepinephrine transporter protein expression between Sham,U+CAO and CAO groups?p>0.05?;There was no significant difference in the expression level of norepinephrine transporter membrane protein in the CAO group compared with the Sham group?p>0.05?,and the expression level of norepinephrine transporter membrane protein in the U+CAO group was down-regulated;The expression of norepinephrine transporter membrane protein was down-regulated in the U+CAO group compared with the CAO group.Conclusion:In the early stage of acute myocardial ischemia,increased cardiac sympathetic activity and changes in the function of norepinephrine transporter in cardiac myocyte membrane can trigger ischemic arrhythmia,antagonizing endogenous N/OFQ receptors is one of the reasons that can decrease cardiac sympathetic activity and regulate the expression of norepinephrine transporter membrane protein,antagonizing endogenous N/OFQ receptors can reduce the occurrence of acute ischemic arrhythmia in rats by reducing cardiac sympathetic activity and regulating norepinephrine transporter membrane protein expression. |
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