吉非替尼是治疗局部晚期非小细胞肺癌的有效方法。然而,它与心脏毒性相关,可能会限制其临床使用。利拉鲁肽,胰高血糖素样肽1受体激动剂,显示出有效的心脏保护作用,其机制尚待阐明。因此,本研究旨在确定利拉鲁肽对吉非替尼引起的心脏损伤的保护作用.成年雄性Wistar大鼠随机分为对照组,利拉鲁肽组(腹膜内注射200µg/kg),吉非替尼组(口服30mg/kg)和利拉鲁肽加吉非替尼组。28天后,收集血液和组织样本进行组织病理学检查,生物化学,基因和蛋白质分析。我们证明吉非替尼治疗(30mg/kg)导致心脏损伤,如组织病理学研究所证明的。此外,血清肌酸激酶-MB(CK-MB),吉非替尼组的N末端B型利钠肽前体(NT-proBNP)和心肌肌钙蛋白I(cTnI)明显升高。用利拉鲁肽预处理(200µg/kg),然而,恢复了血清标志物的升高,并减轻了吉非替尼引起的心脏损伤。此外,利拉鲁肽提高了抗氧化剂(超氧化物歧化酶)的基因和蛋白质水平,并降低了氧化应激标志物(NF-κB)。机械上,利拉鲁肽通过上调存活激酶(ERK1/2和Akt)和下调应激激活激酶(JNK和P38)提供保护。在这项研究中,我们提供的证据表明,利拉鲁肽通过其抗氧化特性和激活存活激酶,保护心脏免受吉非替尼诱导的心脏损伤.
Gefitinib is an effective treatment for patients with locally advanced non-small cell lung cancer. However, it is associated with cardiotoxicity that can limit its clinical use. Liraglutide, a glucagon-like peptide 1 receptor agonist, showed potent cardioprotective effects with the mechanism is yet to be elucidated. Therefore, this study aimed to determine the efficiency of liraglutide in protecting the heart from damage induced by gefitinib. Adult male Wistar rats were randomly divided into control group, liraglutide group (200 µg/kg by i.p. injection), gefitinib group (30 mg/kg orally) and liraglutide plus gefitinib group. After 28 days, blood and tissue samples were collected for histopathological, biochemical, gene and protein analysis. We demonstrated that gefitinib treatment (30 mg/kg) resulted in cardiac damage as evidenced by histopathological studies. Furthermore, serum Creatine kinase-MB (CK-MB), N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac Troponin-I (cTnI) were markedly elevated in gefitinib group. Pretreatment with liraglutide (200 µg/kg), however, restored the elevation in serum markers and diminished gefitinib-induced cardiac damage. Moreover, liraglutide improved the gene and protein levels of anti-oxidant (superoxide dismutase) and decreased the oxidative stress marker (NF-κB). Mechanistically, liraglutide offered protection through upregulation of the survival kinases (ERK1/2 and Akt) and downregulation of stress-activated kinases (JNK and P38). In this study, we provide evidence that liraglutide protects the heart from gefitinib-induced cardiac damage through its anti-oxidant property and through the activation of survival kinases.