Abstract
Objective To evaluate the effect of penehychdine hydrochloride pretreatment on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway during myocardial ischemia-reperfusion(I/R)in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-240 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), myocardial I/R group and penehyelidine hydrochloride pretreatment group (group PHC). Myocardial I/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.At 30 min before ischemia, penehyelidine hydrochloride 2 mg/kg was injected intraperitoneally in group PHC, and the anterior descending branch of left coronary artery was only exposed but not ligated in group S. Rats were sacrificed at the end of reperfusion, and hearts were removed for measurement of the myocardial infarct size(by 2, 3, 5-triphenyltetrazolium chloride staining), cell apoptosis (by TUNEL) and expression of Nrf2, heme oxygenase-1(HO-1), NQO1 and γ-glutamylcysteine synthetase(γ-GCS) protein and mRNA (by using Western blot or real-time fluorescence quantitative polymerase chain reaction). The percentage of myocardial infarct size and apoptosis index were calculated. Results Compared with group S, the percentage of myocardial infarct size and apoptosis index were significantly increased, and the expression of Nrf2, HO-1, NQO1 and γ-GCS protein and mRNA was down-regulated in I/R and PHC groups (P<0.05). Compared with group I/R, the percentage of myocardial infarct size and apoptosis index were significantly decreased, and the expression of Nrf2, HO-1, NQO1 and γ-GCS protein and mRNA was up-regulated in group PHC (P<0.05). Conclusion Penehyclidine hydrochloride pretreatment attenuates myocardial I/R injury through activating Nrf2-ARE signaling pathway in rats. Key words: Cholinergic antagonists; Myocardial reperfusion injury; Nuclear factor-E2 related factor 2; Response elements; Signal transduction
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