Liraglutide directly protects cardiomyocytes against reperfusion injury possibly via modulation of intracellular calcium homeostasis.
Liraglutide directly protects cardiomyocytes against reperfusion injury possibly via modulation of intracellular calcium homeostasis.
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利拉鲁肽可能通过调节细胞内钙稳态来直接保护心肌细胞免受再灌注损伤。
DOI：
10.11909/j.issn.1671-5411.2017.01.008
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Chen YD
中科院分区：
文献类型：
--
作者：
Hu SY;Zhang Y;Zhu PJ;Zhou H;Chen YD
利拉鲁肽是胰高血糖素样肽-1受体激动剂，用于治疗2型糖尿病患者。我们之前的研究表明，利拉鲁肽通过改善接受经皮冠状动脉介入治疗的急性心肌梗死患者的内皮功能来保护心脏功能。本研究将研究利拉鲁肽是否可以对心肌细胞的再灌注损伤产生直接保护作用。体外实验采用H9 C2细胞和新生大鼠心室肌细胞进行模拟缺氧/复氧（H/R）诱导。TUNEL法检测心肌细胞凋亡。JC-1法测定线粒体膜电位（Δ Km），DHE法测定细胞内活性氧（ROS）。Fura-2/AM测定细胞内钙离子浓度和钙瞬变。免疫荧光染色检测肌浆网Ca ~（2+）-ATP酶（SERCA 2a）的表达水平。在体实验中，分别采用TUNEL法和免疫荧光法检测心肌细胞凋亡和SERCA 2a的表达。体外利拉鲁肽抑制心肌细胞凋亡对抗H/R。利拉鲁肽组心肌细胞的Δ λ m高于H/R组。H/R增加了H9 C2细胞中的ROS产生，利拉鲁肽可减弱该作用。与H/R组相比，利拉鲁肽显著降低了Ca 2+超载，改善了钙瞬变。免疫荧光染色结果显示，利拉鲁肽促进SERCA 2a表达，H/R组SERCA 2a表达降低。在缺血/再灌注大鼠心脏中，与H/R组相比，利拉鲁肽显著减弱细胞凋亡，增加SERCA 2a表达。利拉鲁肽可能通过调节细胞内钙稳态直接保护心肌细胞免受再灌注损伤。
Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perform direct protective effects on cardiomyocytes against reperfusion injury. In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation (H/R) induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2+ concentration and calcium transient. Immunofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. ΔΨm of cardiomyocytes was higher in liraglutide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2+ overload and improved calcium transient compared with H/R group. Immunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.