Department of Neurology Laboratory, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China; Department of Intensive Care Unit (ICU), Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China.
Department of Emergency Medicine, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China; Department of Intensive Care Unit (ICU), Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China.
J Stroke Cerebrovasc Dis. 2024 Aug;33(8):107628. doi: 10.1016/j.jstrokecerebrovasdis.2024.107628. Epub 2024 Feb 9.
Ischemic stroke (IS) is a leading cause of morbidity and mortality globally. This study aimed to investigate the role of exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) treated with Musk Ketone (Mus treated-Exo) in the development of IS injury.
BMSCs were pretreated with 10 μM Mus for 36 h, and Exo derived from these Mus-treated BMSCs (Mus-treated Exo) were extracted. Rats with middle cerebral artery occlusion (MCAO) were administered either 2 mg/kg of control Exo (Ctrl-Exo), 2 mg/kg of Mus treated-Exo, or 10 μM Mus. Neurological deficit and cerebral infarction in the MCAO rats were assessed utilizing neurological scores and TTC staining. Neuronal apoptosis, activation of microglia/macrophages, and inflammation were evaluated through TUNEL staining, immunofluorescence staining, and western blot analysis, respectively.
Our findings revealed that Mus-treated Exo possessed a more pronounced neuroprotective effect on MCAO rats when compared to Ctrl-Exo and Mus treatment alone. Specifically, Mus treated-Exo effectively ameliorated neurological function, reduced the volume of cerebral infarction, and diminished hemispheric swelling in MCAO rats. Moreover, it inhibited neuronal apoptosis and activation of microglia/macrophages, promoted the expression of the anti-apoptotic protein Bcl-2 while decreasing the expression of pro-apoptotic protein Bax, Cleaved-caspase 3, and pro-inflammatory factors IL-6 and COX-2.
The findings imply that Mus treated-Exo could confer neuroprotection in rats affected by IS, potentially by attenuating apoptosis and neuroinflammation. The underlying mechanisms, however, warrant further investigation. Mus treated-Exo shows potential as a new therapeutic strategy for IS.
缺血性脑卒中（IS）是全球发病率和死亡率的主要原因。本研究旨在探讨经麝香酮（Mus 处理）处理的骨髓间充质干细胞（BMSC）衍生的外泌体（Exo）在 IS 损伤发展中的作用。
用 10 μM Mus 预处理 BMSC 36 h，提取来自这些 Mus 处理的 BMSC 的 Exo（Mus 处理的 Exo）。给予大脑中动脉闭塞（MCAO）大鼠 2 mg/kg 的对照 Exo（Ctrl-Exo）、2 mg/kg 的 Mus 处理的 Exo 或 10 μM Mus。利用神经评分和 TTC 染色评估 MCAO 大鼠的神经功能缺损和脑梗死。通过 TUNEL 染色、免疫荧光染色和 Western blot 分析分别评估神经元凋亡、小胶质细胞/巨噬细胞激活和炎症。
与 Ctrl-Exo 和 Mus 单独处理相比，Mus 处理的 Exo 对 MCAO 大鼠具有更显著的神经保护作用。具体而言，Mus 处理的 Exo 有效改善了 MCAO 大鼠的神经功能，减少了脑梗死的体积，并减轻了 MCAO 大鼠的半球肿胀。此外，它抑制了神经元凋亡和小胶质细胞/巨噬细胞的激活，促进了抗凋亡蛋白 Bcl-2 的表达，同时降低了促凋亡蛋白 Bax、Cleaved-caspase 3 和促炎因子 IL-6 和 COX-2 的表达。
这些发现表明，Mus 处理的 Exo 可能通过减轻细胞凋亡和神经炎症为 IS 大鼠提供神经保护。然而，其潜在机制需要进一步研究。Mus 处理的 Exo 显示出作为 IS 的一种新的治疗策略的潜力。
