Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats
Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats
复制标题
西格列汀可减轻糖尿病大鼠左心室的心肌重塑并改善心脏舒张功能障碍。
DOI：
10.1016/j.jphs.2014.12.007
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发表时间：
2015-03-01
影响因子：
3.5
通讯作者：
Zhang, Mei
中科院分区：
文献类型：
--
作者：
Liu, Yu-Sheng;Huang, Zhi-Wei;Zhang, Mei
目的：西格列汀是一种二肽基肽酶IV(DPP-IV)抑制剂，具有提高血清胰高血糖素样肽-1(GLP-1)水平的生物学作用。因此，我们试图确定西格列汀对糖尿病大鼠心肌炎症、胶原代谢、脂质含量和心肌细胞凋亡的影响。材料和方法：以小剂量链脲佐菌素和高脂饮食诱导2型糖尿病大鼠模型。通过心电图、超声心动图和血液分析评价糖尿病大鼠的特点。通过组织病理学分析、逆转录聚合酶链式反应(RT-PCR)和免疫印迹法检测与细胞凋亡相关的心肌炎症、纤维化、心肌细胞密度、脂质蓄积和受体相互作用蛋白激酶3(RIP3)水平，以评价西格列汀对左室心肌重构的影响。结果：糖尿病大鼠心肌肥大或凋亡、炎症、脂质蓄积、心肌纤维化、胶原含量升高、RIP3过度表达和左心功能不全。西格列汀可逆转心肌组织中RIP3的过度表达，减轻细胞凋亡。西格列汀可显著改善糖尿病大鼠左室收缩压和+dp/dtmax，降低E/E‘比值、左室舒张末压、-dp/dtmax和Tau。结论：西格列汀可能通过抑制糖尿病大鼠心肌细胞凋亡、炎症反应、脂质蓄积和心肌纤维化而发挥心肌保护作用，可能具有改善糖尿病左心功能的作用。(C)2014年日本药理学会。爱思唯尔B.V.制作和主办。保留所有权利。
Objective: Sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats.Materials and methods: The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis. Cardiac inflammation, fibrosis, cardiomyocyte density, lipid accumulation, and receptor-interacting protein kinase 3 (RIP3) level, related to apoptosis, were detected by histopathologic analysis, RT-PCR and western blot analysis to evaluate the effects of sitagliptin on myocardial remodeling of the left ventricle.Results: Diabetic rats showed myocardial hypertrophy or apoptosis, inflammation, lipid accumulation, myocardial fibrosis, elevated collagen content, RIP3 overexpression, and left-ventricular dysfunction. Sitagliptin could reverse the overexpression of RIP3 and alleviate cellular apoptosis in myocardial tissues. It could significantly improve left-ventricular systolic pressure and +dp/dt max, reduce the E/E' ratio, left ventricular end diastolic pressure, -dp/dt max and Tau in diabetic rats.Conclusions: Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes. (C) 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.