Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3β-HIF-1α signaling pathway.

IF 1.1 4区医学 Q3 SURGERY

Acta cirurgica brasileira Pub Date : 2022-01-01 DOI:10.1590/acb371004

Mei Qian, Yang Liu

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Abstract

Purpose: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury.

Methods: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3β/GSK-3β were measured in heart homogenates. LY294002 was employed as PI3K inhibitor.

Results: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3β/GSK-3β. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate.

Conclusions: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3β and HIF-1α signaling pathway.

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阿瑞吡坦在缺血再灌注心肌损伤大鼠模型中的心脏保护作用:PI3K-AkT-GSK-3β-HIF-1α信号通路的作用

目的:探讨阿瑞吡坦在大鼠缺血再灌注损伤模型中的心脏保护作用及其机制。方法:采用Langendorff仪对Wistar雄性白化大鼠离体心脏进行缺血再灌注损伤。通过测定冠状动脉流出液中乳酸脱氢酶1和CK-MB的释放来评估心肌损伤程度。大鼠在分离心脏前分别给予阿瑞吡坦(5、10和20 mg/kg)。损伤后，测定心脏匀浆中HIF-1α、p-AkT、p-GSK-3β/GSK-3β的水平。LY294002作为PI3K抑制剂。结果:缺血再灌注大鼠心肌损伤显著，HIF-1α、p-AkT水平降低，p-GSK-3β/GSK-3β比值降低。阿瑞吡坦减轻心肌损伤，恢复生化变化呈剂量依赖性。LY294002(10和20 mg/kg)预处理可消除阿瑞吡坦介导的心脏保护作用，恢复心脏匀浆中的生化参数。结论:阿瑞吡坦可能与激活PI3K-AkT-GSK-3β和HIF-1α信号通路有关，可有效预防缺血再灌注引起的心肌损伤。

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