JOURNAL ARTICLE

Ischaemic preconditioning-induced serum exosomes protect against myocardial ischaemia/reperfusion injury in rats by activating the PI3K/AKT signalling pathway

Jie Zhang, Xijiang Zhang
Cell Biochemistry and Function 2020 August 7
32767595
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.

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