{"title":"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","authors":"Mei Qian, Yang Liu","doi":"10.1590/acb371004","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":6992,"journal":{"name":"Acta cirurgica brasileira","volume":"37 10","pages":"e371004"},"PeriodicalIF":1.1000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762430/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3β-HIF-1α signaling pathway.\",\"authors\":\"Mei Qian, Yang Liu\",\"doi\":\"10.1590/acb371004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":6992,\"journal\":{\"name\":\"Acta cirurgica brasileira\",\"volume\":\"37 10\",\"pages\":\"e371004\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762430/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta cirurgica brasileira\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/acb371004\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta cirurgica brasileira","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/acb371004","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"SURGERY","Score":null,"Total":0}
Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3β-HIF-1α signaling pathway.
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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