PDF(Pubmed)
Abstract：
One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 μg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM.
摘要：
治疗糖尿病性心肌病的可能候选者之一是利拉鲁肽，胰高血糖素样肽-1受体(GLP1R)激动剂。在这项研究中,研究了利拉鲁肽对链脲佐菌素诱导的2型糖尿病大鼠整合素连接激酶(ILK)相关PI3K/AKT轴的影响.24只Wistar白化病大鼠分为四个不同的组，两组均使用高脂饮食和链脲佐菌素诱导2型。未经处理的对照组大鼠在6周内给予0.9%NaCl溶液,治疗组给予0.9%NaCl3周,然后皮下注射利拉鲁肽（150μg/kg），持续3周。在利拉鲁肽治疗的糖尿病组中，心脏体重比显著降低，心脏生物标志物的水平，肌钙蛋白I和肌酸激酶-MB，得到改善；抗氧化酶的活性，谷胱甘肽过氧化物酶和超氧化物歧化酶，增加；丙二醛水平降低。蛋白质印迹和免疫组织化学研究显示ILK水平升高，P-PI3K,P-AKT,和BCL2，以及半胱天冬酶3，BAX，P-PTEN,表明心肌细胞凋亡的缓解。我们的结果表明，利拉鲁肽，通过瞄准GLP1Rs，增强ILK/PI3K/AKT/PTEN途径中蛋白质的表达，从而在DCM大鼠中发挥其心脏保护作用。
