MM. Taizhou Second People's Hospital - Department of Pharmacy - Taizhou, China.
MM. Mudanjiang Medical University - Teaching Materials Section - Mudanjiang, China.
Acta Cir Bras. 2022 Dec 19;37(10):e371004. doi: 10.1590/acb371004. eCollection 2022.
The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury.
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.
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.
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.
本研究探讨了阿瑞匹坦诱导的缺血再灌注损伤大鼠模型中心脏保护作用的机制。
采用 Langendorff 装置对 Wistar 雄性白化大鼠的离体心脏进行缺血再灌注损伤。通过测量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。在分离心脏之前，用阿瑞匹坦（5、10 和 20mg/kg）对大鼠进行预处理。损伤后，在心脏匀浆中测量 HIF-1α、p-AkT、p-GSK-3β/GSK-3β 的水平。LY294002 被用作 PI3K 抑制剂。
缺血再灌注导致明显的心肌损伤，并降低了 HIF-1α、p-AkT 和 p-GSK-3β/GSK-3β 比值。阿瑞匹坦呈剂量依赖性减轻心肌损伤并恢复生化变化。LY294002（10 和 20mg/kg）预处理消除了阿瑞匹坦介导的心脏保护作用，并恢复了心脏匀浆中的生化参数。
阿瑞匹坦可能有效预防缺血再灌注引起的心肌损伤，这可能是由于激活了 PI3K-AkT-GSK-3β 和 HIF-1α 信号通路。
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