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甘丙肽减轻链脲佐菌素诱导糖尿病大鼠的心肌缺血/再灌注损伤

Galanin Reduces Myocardial Ischemia/Reperfusion Injury in Rats with Streptozotocin Diabetes.

作者信息

Studneva I M, Serebryakova L I, Veselova O M, Dobrokhotov I V, Palkeeva M E, Avdeev D V, Molokoedov A S, Sidorova M V, Pisarenko O I

机构信息

Chazov National Medical Research Center of Cardiology, Moscow 121552 Russian Federation.

出版信息

Acta Naturae. 2025 Jan-Mar;17(1):78-86. doi: 10.32607/actanaturae.27506.

Abstract

Most clinical studies confirm the negative impact diabetes mellitus (DM) has on the course and outcome of cardiovascular complications caused by a myocardial ischemia-reperfusion injury (IRI). In this regard, the search for new approaches to IRI treatment in diabetic myocardium is of undeniable value. The aim of this work was to study the effect of galanin (G) on the size of myocardial infarct (MI), on mitochondrial functions, and on the energy state in the area at risk (AAR) in rats with type 1 diabetes mellitus (DM1) subjected to regional myocardial ischemia and reperfusion. Rat G was obtained by solid-phase synthesis using the Fmoc strategy and purified by HPLC. DM1 was induced by streptozotocin administration. Myocardial IRI was modeled by occlusion of the left anterior descending coronary artery and subsequent reperfusion. G at a dose of 1 mg/kg was administered intravenously before reperfusion. G decreased MI size and plasma creatine kinase MB (CK-MB) activity in DM rats by 40 and 28%, respectively. G injection improved mitochondrial respiration in saponin-skinned fibers in the AAR: namely, the maximal ADP-stimulated state 3, respiratory control, and the functional relationship between the mitochondrial CK-MB and oxidative phosphorylation. G provided significantly higher ATP levels, total adenine nucleotide pool, and adenylate energy charge of cardiomyocytes. It also reduced total creatine loss in myocardial AAR in DM rats. The results suggest there is a possibility of therapeutic use of G in myocardial IRI complicated by DM1.

摘要

大多数临床研究证实,糖尿病(DM)对心肌缺血再灌注损伤(IRI)所致心血管并发症的病程及转归具有负面影响。就此而言,探寻糖尿病心肌中IRI的新治疗方法具有不可否认的价值。本研究旨在探讨甘丙肽(G)对1型糖尿病(DM1)大鼠局部心肌缺血再灌注后心肌梗死(MI)面积、线粒体功能及危险区域(AAR)能量状态的影响。大鼠G通过采用Fmoc策略的固相合成法获得,并经高效液相色谱法纯化。通过注射链脲佐菌素诱导建立DM1模型。通过结扎左冠状动脉前降支并随后再灌注来模拟心肌IRI。在再灌注前静脉注射1 mg/kg剂量的G。G使糖尿病大鼠的MI面积和血浆肌酸激酶MB(CK-MB)活性分别降低了40%和28%。注射G改善了AAR中皂素透化纤维的线粒体呼吸:即最大ADP刺激的状态3、呼吸控制以及线粒体CK-MB与氧化磷酸化之间的功能关系。G使心肌细胞的ATP水平、总腺嘌呤核苷酸池和腺苷酸能荷显著升高。它还减少了糖尿病大鼠心肌AAR中的总肌酸损失。结果表明,G有可能用于治疗并发DM1的心肌IRI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ff/12011184/e942901b5cb7/AN20758251-17-01-078-g001.jpg

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