Antagonism of endogenous nociceptin/orphanin FQ inhibits reperfusion-induced arrhythmias by down-regulating microRNA-1 in rats / 中国药理学通报

ABSTRACT

Aim: To investigate the effect of endogenous nociceptin/orphanin FQ(N/OFQ) on arrhythmias induced by myocardial ischemia/reperfusion (I/R) in rats and the role of microRNA-1 (miR-1) in it. Methods: Twenty-four Sprague-Dawley rats were randomly divided into sham-operation group (Sham group), ischemia/reperfusion group (I/R group) and the pretreatment of N/OFQ receptor antagonist (UFP-101) group(U + I/R group). The model of myocardial ischemia/reperfusion was prepared by ligating the left anterior descending branch of the coronary artery of rats. The incidence and arrhythmogenic scores during reperfusion in rats were recorded and analysed. The myocardium at the risk of ischemia was collected at 120 min after reperfusion. MiR-1, GJA1 and KCNJ2 levels were detected by qRT-PCR and Cx43 and kir2. 1 protein levels were detected by Western blot. Results: Antagonism of endogenous N/OFQ could significantly reduce reperfusion arrhythmias and arrhythmogenic scores, compared with I/R group (P < 0. 01). The qRT-PCR and Western blot results suggested that compared with sham group, miR-1 expression significantly increased in I/R group(P < 0. 01), while the expression of Cx43, Cx43 mRNA and kir2. 1 decreased(P< 0. 05); compared with I/R group, pretreatment with UFP-101 led to reduction of miR-1 (P<0. 05) and rise of Cx43 and kir2. 1 (P < 0. 05). Conclusions: Endogenous N/OFQ up-regulates miR-1 and inhibits the expression of Cx43 and kir2. 1 proteins, leading to reperfusion arrhythmias in rats.