Objective: To investigate whether remote ischemic preconditioning (RIPC) plasma exosomes enhance the tolerance of nerve cells to hypoxia / ischemia by regulating autophagy pathway. Methods: Serum samples were collected from stroke patients and healthy subjects before and after RIPC intervention. Exosomes were extracted and co-cultured with SH-SY5 Y human neuroblastoma cells, and then oxygen-glucose deprivation (OGD) stimulation was applied to the cell model. The protein expression levels of apoptosis markers (Bcl-2, BAX) and autophagy markers (Beclin1, LC3) were determined by Western blot. The degree of cell membrane integrity damage was analyzed by lactate dehydrogenase (LDH) release assay. The formation of autophagosomes was observed by LC3-GFP fluorescence transfection system combined with laser confocal microscopy. Results: The intervention of RIPC exosomes in stroke patients and healthy adults significantly up-regulated Bcl-2 (P＜0.05) and down-regulated BAX (P＜0.05). Activation of autophagy pathway showed increased expression of Beclin1, increased LC3-II+LC3-I/β-actin (P＜0.05) and increased number of autophagosomes. The LDH release rate decreased (P＜0.05), and the protective effect of serum exosomes after RIPC was better than that of untreated serum exosomes. Conclusion: Serum exosomes after RIPC enhance hypoxia/ischemia tolerance of nerve cells by regulating autophagy activation and apoptosis inhibition, which may be one of the mechanisms of RIPC neuroprotection.
LI Ruixue
,
WANG Xiaojie
,
XIE Yabin
,
SHAO Guo
. Study on the mechanism of remote ischemic preconditioning exosomes enhancing neurotolerance through autophagy[J]. Journal of Baotou Medical College, 2026
, 42(6)
: 20
-25
.
DOI: 10.16833/j.cnki.jbmc.2026.06.004
[1] Zhao W, Li S, Ren C, et al. Remote ischemic conditioning for stroke: clinical data, challenges, and future directions [J]. Ann Clin Transl Neurol, 2019, 6(1): 186-196.
[2] Rajsic S, Gothe H, Borba HH, et al. Economic burden of stroke: a systematic review on post-stroke care [J]. Eur J Health Econ, 2019, 20(1): 107-134.
[3] Cheng X, Zhang F, Li J, et al. Galuteolin attenuates cerebral ischemia/reperfusion injury in rats via anti-apoptotic, anti-oxidant, and anti-inflammatory mechanisms [J]. Neuropsychiatr Dis Treat, 2019, 15: 2671-2680.
[4] Zhang X, Jizhang Y, Xu X, et al. Protective effects of remote ischemic conditioning against ischemia/reperfusion-induced retinal injury in rats [J]. Vis Neurosci, 2014, 31(3): 245-252.
[5] Yamaguchi T, Izumi Y, Nakamura Y, et al. Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction [J]. Int J Cardiol, 2015, 178: 239-246.
[6] White E. Deconvoluting the context-dependent role for autophagy in cancer [J]. Nat Rev Cancer, 2012, 12(6): 401-410.
[7] Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases [J]. EMBO J, 2021, 40(19): e108863.
[8] Li Z, Cui X, Lv H, et al. Remote ischemic postconditioning attenuates damage in rats with chronic cerebral ischemia by upregulating the autophagolysosome pathway via the activation of TFEB [J]. Exp Mol Pathol, 2020, 115: 104475.
[9] 张志勇, 王小洁, 邵国.RIPC通过血浆外泌体增加神经细胞低氧缺血耐受[J].中国比较医学杂志, 2025, 35(11):1-10.
[10] Billah M, Ridiandries A, Allahwala U, et al. Circulating mediators of remote ischemic preconditioning: search for the missing link between non-lethal ischemia and cardioprotection [J]. Oncotarget, 2019, 10(2): 216-244.
[11] Hao Y, Xin M, Feng L, et al. Review Cerebral Ischemic Tolerance and Preconditioning: Methods, Mechanisms, Clinical Applications, and Challenges [J]. Front Neurol, 2020, 11: 812.
[12] Yin W, Ma H, Qu Y, et al. Exosomes: the next-generationtherapeutic platform for ischemic stroke [J]. Neural Regen Res, 2025, 20(5): 1221-1235.
[13] Su J, Zhang T, Wang K, et al. Autophagy activation contributes to the neuroprotection of remote ischemic perconditioning against focal cerebral ischemia in rats [J]. Neurochem Res, 2014, 39(11): 2068-2077.
[14] Deng YH, He HY, Yang LQ, et al. Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke [J]. Neural Regen Res, 2016, 11(7): 1108-1114.
