Ischaemia/reperfusion (I/R) injury can lead to severe arrhythmia and aggravate myocardial damage. Exosomes are small‐membrane vesicles that play a protective role in myocardial I/R injury. This study aimed to explore the protective effects of ischaemic preconditioning (IPC)‐induced serum exosomes (IPC‐Exo) on myocardial I/R injury in rats and its underlying mechanism. Serum exosomes were extracted from IPC rats and quantified using a bicinchoninic acid assay kit. IPC‐Exo (50 μg) was injected into the infarcted myocardium immediately after ligation. Rats were randomly divided into Sham, I/R, IPC‐Exo + I/R, I/R + LY294002, and I/R + IPC‐Exo + LY294002 groups. Haemodynamic parameters were measured by physiological recording. Transthoracic echocardiography was used to detect cardiac function. The serum levels of creatine kinase isomer‐MB, lactate dehydrogenase, aspartate transaminase, tumour necrosis factor‐alpha, interleukin (IL)‐1β, and IL‐10 were detected by enzyme‐linked immunosorbent assay. Triphenyl tetrazolium chloride staining was used to measure the myocardial infarct size. Apoptosis in myocardial tissues was detected by TUNEL staining. Western blotting was used to detect the levels of PI3K/AKT and apoptosis‐related proteins. Our results showed that treatment with IPC‐Exo ameliorated cardiac function and reduced inflammatory factor production, cardiomyocyte apoptosis, and myocardial infarct size. Moreover, IPC‐Exo treatment promoted the protein expression of Bcl‐2, p‐PI3K, and p‐AKT but inhibited that of caspase‐3 and Bax. However, treatment with LY294002 significantly reversed that IPC‐Exo‐induced increase in p‐PI3K and p‐AKT levels, improvement of haemodynamics, and decrease of inflammatory factor production and apoptosis in the I/R + IPC‐Exo group. Taken together, our results suggest that IPC‐Exo may alleviate I/R injury via activating the PI3K/AKT signalling pathway.

中文翻译：

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缺血预处理诱导的血清外来体通过激活PI3K / AKT信号通路来保护大鼠免于心肌缺血/再灌注损伤

缺血/再灌注（I / R）损伤可导致严重的心律不齐并加重心肌损害。外泌体是在心肌I / R损伤中起保护作用的小膜囊泡。本研究旨在探讨缺血预处理（IPC）诱导的血清外泌体（IPC-Exo）对大鼠心肌I / R损伤的保护作用及其潜在机制。从IPC大鼠中提取血清外泌体，并使用二辛可宁酸测定试剂盒进行定量。结扎后立即将IPC-Exo（50μg）注入梗塞的心肌中。将大鼠随机分为假手术，I / R，IPC-Exo + I / R，I / R + LY294002和I / R + IPC-Exo + LY294002组。通过生理记录测量血流动力学参数。经胸超声心动图检查可检测心脏功能。血清肌酸激酶异构体MB 酶联免疫吸附法检测了乳酸脱氢酶，天冬氨酸转氨酶，肿瘤坏死因子-α，白介素（IL）-1β和IL-10。三苯基氯化四唑鎓染色用于测量心肌梗塞大小。通过TUNEL染色检测心肌组织中的细胞凋亡。蛋白质印迹用于检测PI3K / AKT和凋亡相关蛋白的水平。我们的结果表明，使用IPC-Exo进行治疗可改善心脏功能，并减少炎症因子的产生，心肌细胞凋亡和心肌梗塞面积。此外，IPC-Exo处理促进了Bcl-2，p-PI3K和p-AKT的蛋白表达，但抑制了caspase-3和Bax的蛋白表达。但是，用LY294002进行的治疗可大大逆转IPC-Exo诱导的p-PI3K和p-AKT水平升高，血流动力学改善，I / R + IPC-Exo组的炎症因子产生和凋亡减少。综上所述，我们的结果表明IPC-Exo可以通过激活PI3K / AKT信号通路减轻I / R损伤。