Objective: To investigate the effects and underlying molecular mechanisms of plasma-derived exosomes from patients with type 2 diabetes mellitus (T2DM) on SH-SY5Y neuronal cells under an oxygen-glucose deprivation (OGD) model. Methods: Plasma exosomes were isolated from healthy individuals and T2DM patients using differential ultracentrifugation. Exosomal markers CD9 and HSP70 were identified via Western blot, and particle size distribution was analyzed using a Zetasizer. The OGD model was established by subjecting cells to glucose-free, low-oxygen conditions for 6 hours followed by 24 hours of reoxygenation. SH-SY5Y cells were divided into six groups: control (C), OGD (G), and exosome-treated groups (C-EXO, C-EXO-T2DM, G-EXO, G-EXO-T2DM). Cell proliferation was assessed using the CCK8 assay. Apoptosis levels were evaluated via flow cytometry and live-cell imaging. Expression of apoptosis-related proteins (spectrin and Bcl-2) was analyzed by Western blot. Results: Exosomal markers CD9 and HSP70 were positively expressed, and exosome diameters ranged from 30 to 150 nm. Co-culture with T2DM-derived plasma exosomes significantly reduced cell viability in the OGD group (P＜0.05), with increased spectrin expression and decreased Bcl-2 expression. Flow cytometry revealed elevated early apoptosis rates induced by T2DM plasma exosomes. Conclusion: T2DM plasma exosomes aggravate neuronal apoptosis under OGD conditions by regulating the Bcl-2/spectrin pathway, suggesting a potential pathogenic role in diabetes-associated stroke.
YOU Yuan
,
JIANG Shuyuan
,
ZHU Hongwei
,
WANG Peng
,
LI Bifei
,
XIE Wei
,
JIA Xiaoe
,
SHAO Guo
,
LIU You
. Effects of plasma exosomes from T2DM patients on OGD-treated SH-SY5Y cells[J]. Journal of Baotou Medical College, 2025
, 41(12)
: 40
-45
.
DOI: 10.16833/j.cnki.jbmc.2025.12.008
[1] Elsharkawy RE, Abdel Azim GS, Osman MA, et al. Peripheral Polyneuropathy and Cognitive Impairment in Type II Diabetes Mellitus[J]. Neuropsychiatr Dis Treat, 2021, 17:627-635.
[2] Wu Y, Ding Y, Tanaka Y, et al. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention[J]. Int J Med Sci, 2014, 11(11):1185-1200.
[3] GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet Neurol, 2024, 23(4):344-381.
[4] Beit-Yannai E, Tabak S, Stamer WD. Physical exosome:exosome interactions[J]. J Cell Mol Med, 2018, 22(3):2001-2006.
[5] Mathivanan S, Fahner CJ, Reid GE, et al. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res[J]. 2012, 40(Database issue):D1241-1244.
[6] Li X, Lian Y, Wu Y, et al. Neonatal Plasma Exosomes Contribute to Endothelial Cell-Mediated Angiogenesis and Cardiac Repair after Acute Myocardial Infarction[J]. Int J Mol Sci, 2023, 24(4):3196.
[7] Li J, Wu G, Li W, et al. Plasma exosomes improve peripheral neuropathy via miR-20b-3p/Stat3 in type I diabetic rats[J]. J Nanobiotechnology, 2023, 21(1):447.
[8] Tao X, Xue Y, Niu R, et al. Comparisons of clinical outcomes between newly diagnosed early- and late-onset T2DM: a real-world study from the Shanghai Hospital Link Database[J]. Endocr Connect, 2024, 13(2):e230474.
[9] Burtscher J, Mallet RT, Burtscher M, et al. Hypoxia and brain aging: Neurodegeneration or neuroprotection[J]. Ageing Res Rev, 2021, 68:101343.
[10] Ouellette J, Lacoste B. From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum[J]. Front Aging Neurosci, 2021, 13:749026.
[11] Cheng C, Chen X, Wang Y, et al. MSCsderived exosomes attenuate ischemia-reperfusion brain injury and inhibit microglia apoptosis might via exosomal miR-26a-5p mediated suppression of CDK6[J]. Mol Med, 2021, 27(1):67.
[12] Zhu ZH, Jia F, Ahmed W, et al. Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke[J]. Neural Regen Res, 2023, 18(2):404-409.
[13] Song Y, Li Z, He T, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124[J]. Theranostics, 2019, 9(10):2910-2923.
[14] Wider J, Undyala VVR, Whittaker P, et al. Remote ischemic preconditioning fails to reduce infarct size in the Zucker fatty rat model of type-2 diabetes: role of defective humoral communication[J]. Basic Res Cardiol, 2018, 113(3):16.
[15] Rizzo MR, Marfella R, Barbieri M, et al. Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients[J]. Diabetes Care, 2010, 33(10):2169-2174.
