左西孟旦减轻模型大鼠离体心脏停灌/再灌注损伤

doi:10.16352/j.issn.1001-6325.2025.01.0065

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (1): 65-69.doi: 10.16352/j.issn.1001-6325.2025.01.0065

左西孟旦减轻模型大鼠离体心脏停灌/再灌注损伤

庞昀婷¹, 任晓爽¹, 包涵¹, 孟凡青¹, 石枫^2*

1.济南市妇幼保健院麻醉科,山东济南 250000;
2.山东中医药大学附属医院胃肠与疝外科,山东济南 250000

收稿日期:2024-09-12 修回日期:2024-11-24 出版日期:2025-01-05 发布日期:2024-12-25
通讯作者: ^*mapstone@126.com
基金资助:
济南市卫生健康委员会科技计划(2023-2-105)

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

PANG Yunting¹, REN Xiaoshuang¹, BAO Han¹, MENG Fanqing¹, SHI Feng^2*

1. Department of Anesthesiology, Jinan Maternal and Child Health Care Hospital, Jinan 250000;
2. Department of Gastroenterology and Hernia Surgery, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China

Received:2024-09-12 Revised:2024-11-24 Online:2025-01-05 Published:2024-12-25
Contact: ^*mapstone@126.com

摘要/Abstract

摘要： 目的探讨左西孟旦对大鼠离体心肌停灌/再灌注过程中环磷酸鸟苷-腺苷酸合成酶/干扰素基因刺激因子(cGAS-STING)信号通路的影响。方法将大鼠分为持续灌注组(CO组)、停灌/再灌注组(SR组)、停灌/再灌注+左西孟旦组(SR-L组)及停灌/再灌注+左西孟旦+STING激活剂DMXAA组(SR-LD组)。分别在平衡灌注末(T0)、再灌注30 min(T₁)和再灌注60 min(T₂)时记录心率(HR)、左室舒张末压(LVEDP)、左室发展压(LVDP)、左室内压最大上升速率(+dp/dt_max)和左室内压最大下降速率(-dp/dt_max)和再灌注心律失常评分分数。Western blot检测cGAS-STING信号通路及自噬相关蛋白表达,氯化三苯基四氮唑(TTC)染色法测定心肌梗死面积百分比。结果与CO组相比,SR组T₁、T₂时HR、LVDP、+dp/dt_max和-dp/dt_max降低,LVEDP升高,再灌注心律失常评分增加,心肌梗死面积百分比增加,心肌组织cGAS、STING蛋白表达升高,LC3 Ⅱ/Ⅰ比值升高,p62降低(P＜0.05);与SR组比较,SR-L组心功能指标改善,心肌组织 cGAS、STING蛋白表达下调,LC3 Ⅱ/Ⅰ比值降低,p62升高(P＜0.05);与SR-L相比,SR-LD组逆转了左西孟旦对心肌损伤的保护作用。结论左西孟旦可能通过抑制cGAS-STING信号通路及下调心肌细胞自噬,改善心功能,减少心肌梗死面积,从而发挥心肌保护作用。

关键词: 左西孟旦, 心肌缺血/再灌注, 自噬, cGAS-STING信号通路

Abstract: 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/dt_max) 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/dt_max, and -dp/dt_max 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.

Key words: levosimendan, myocardial ischemia-reperfusion, autophagy, cGAS-STING signaling pathway

中图分类号:

R453

庞昀婷, 任晓爽, 包涵, 孟凡青, 石枫. 左西孟旦减轻模型大鼠离体心脏停灌/再灌注损伤[J]. 基础医学与临床, 2025, 45(1): 65-69.

PANG Yunting, REN Xiaoshuang, BAO Han, MENG Fanqing, SHI Feng. Levosimendan attenuates suspension-reperfusion injury in isolated hearts of rat models[J]. Basic & Clinical Medicine, 2025, 45(1): 65-69.

参考文献

[1] Basir MB, Lemor A, Gorgis S, et al. Vasopressors independently associated with mortality in acute myocardial infarction and cardiogenic shock[J]. Catheter Cardiovasc Interv, 2022, 99:650-657. doi: 10.1002/ccd.29895.
[2] Popov SV, Mukhomedzyanov AV, Voronkov NS, et al. Regulation of autophagy of the heart in ischemia and reperfusion[J]. Apoptosis, 2023, 28:55-80. doi: 10.1007/s10495-022-01786-1.
[3] Huang CQ, Andres AM, Ratliff EP, et al. Precondition-ing involves selective mitophagy mediated by Parkin and p62/SQSTM1[J]. PLoS One, 2011, 6:e20975. doi:10.1371/journal.pone.0020975.
[4] Hopfner KP, Hornung V. Molecular mechanisms and cellular functions of cGAS-STING signalling[J]. Nat Rev Mol Cell Biol, 2020,21:501-521. doi:10.1038/s41580-020-0244-x.
[5] Papp Z, Agostoni P, Alvarez J, et al. Levosimendan efficacy and safety: 20 years of SIMDAX in clinical use[J]. J Cardiovasc Pharmacol, 2020, 76:4-22. doi: 10.1097/FJC.0000000000000859.
[6] Vasileios L, Efstratios K, Nikolaos T, et al. The coadministration of levosimendan and exenatide offers a significant cardioprotective effect to isolated rat hearts against ischemia/reperfusion injury[J]. J Cardiovasc Dev Dis, 2022, 9:263-292. doi: 10.3390/jcdd9080263.
[7] He L, Hao S, Wang Y, et al. Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction[J]. Biomed Pharmacother, 2019, 114:108837. doi: 10.1016/j.biopha.2019.108837.
[8] Walker MJ, Curtis MJ, Hearse DJ, et al. The lambeth conventions: guidelines for the study of arrhythnfias in ischaemia infarction and reperfusion[J]. Cardiovase Res, 1988, 22: 447-455. doi: 10.1093/cvr/22.7.447.
[9] Louhelainen M, Vahtola E, Kaheinen P, et al. Effects of levosimendan on cardiac remodeling and cardiomyo-cyte apoptosis in hypertensive Dahl/Rapp rats[J]. Br. J.Pharmacol, 2007,150: 851-861. doi: 10.1038/sj.bjp.0707157.
[10] Li G, Zhao X, Zheng Z, Zhang. cGAS-STING pathway mediates activation of dendritic cell sensing of immuno-genic tumors[J]. Cell Mol Life Sci, 2024, 81:149. doi: 10.1007/s00018-024-05191-6.
[11] Li JK, Song ZP, Hou XZ. Scutellarin ameliorates ischemia/reperfusion injury-induced cardiomyocyte apoptosis and cardiac dysfunction via inhibition of the cGAS-STING pathway[J]. Exp Ther Med, 2023, 25:155. doi: 10.3892/etm.2023.11854.
[12] 江罗佳, 许海波. 白藜芦醇缓解低氧/复氧诱导的TCMK1细胞线粒体自噬[J]. 基础医学与临床, 2022, 42:1709-1715. doi: 10.16352/j.issn.1001-6325.2022.11.1709.
[13] Song L, Jian MR, Shi YL, et al. Resveratrol inhibits autophagy against myocardial ischemia-reperfusion injury through the DJ-1/MEKK1/JNK pathway[J]. Eur J Pharmacol, 2023, 951:175748. doi: 10.1016/j.ejphar.2023.175748.
[14] Qin GW, Lu P, Peng L, et al. Ginsenoside Rb1 inhibits cardiomyocyte autophagy via PI3K/Akt/mTOR signaling pathway and reduces myocardial ischemia/reperfusion Injury[J]. Am J Chin Med, 2021, 49:1913-1927. doi: 10.1142/S0192415X21500907.
[15] Liu D, Wu H, Wang CG, et al. STING directly activates autophagy to tune the innate immuneresponse[J]. Cell Death Differ, 2019, 26:1735-1749. doi: 10.1038/s41418-018-0251-z. doi: 10.1038/s41418-018-0251-z.

左西孟旦减轻模型大鼠离体心脏停灌/再灌注损伤

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

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