Jichu yixue yu linchuang (Jan 2025)

Levosimendan attenuates suspension-reperfusion injury in isolated hearts of rat models

  • PANG Yunting, REN Xiaoshuang, BAO Han, MENG Fanqing, SHI Feng

DOI
https://doi.org/10.16352/j.issn.1001-6325.2025.01.0065
Journal volume & issue
Vol. 45, no. 1
pp. 65 – 69

Abstract

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Objective To investigate the effect of levosimendan on the cyclic guanosine monophosphate-adenosin monophosphate synthase-interferon gene stimulating factor (cGAS-STING) signaling pathway during suspension-reperfusion in isolated rat myocardium. Methods The rats were divided into four groups (n=12) using random number table: continuous perfusion group (CO group),suspension-reperfusion group(SR group),suspension-reperfusion+levosimendan group (SR-L group), and suspension-reperfusion+levosimendan+STING activator: DMXAA group (SR-LD group). Heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), maximum rate of increase in left ventricular pressure (+dp/dtmax) and maximum rate of decrease in left ventricular pressure (-dp/dtmax), and Reperfusion Arrhythmia scores were recorded at the end of equilibrium perfusion (T0), 30 min of reperfusion (T1), and 60 min of reperfusion (T2) respectively. Western blot was used to detect cGAS-STING signaling pathway and autophagy-related protein expression. The size of myocardial infarction was measured by using triphenyl tetrazolium chloride (TTC). Results Compared with CO group, SR group had decreased HR, LVDP, +dp/dtmax, and -dp/dtmax at T1 and T2, increase of LVEDP,Reperfusion Arrhythmia score , percentage of myocardial infarcted area, expression of myocardial tissue cGAS and STING proteins and increased LC3 Ⅱ/Ⅰ ratio, while p62 decreased (P＜0.05); compared with SR group, SR-L group cardiac function indexes improved, myocardial tissue cGAS, STING protein expression was down-regulated, LC3 Ⅱ/Ⅰ ratio was decreased, and p62 was elevated (P＜0.05); SR-LD group reversed the improvement of myocardial injury by levosimendan compared with SR-L. Conclusions Levosimendan may protect myocardial tissue by inhibiting the cGAS-STING signaling pathway, down-regulating cardiomyocyte autophagy and reducing myocardial infarction size, so to improve cardial function.

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