Exosomes containing miR-451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury.
Exosomes containing miR-451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury.
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DOI：
10.1111/cns.13612
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发表时间：
2021-05
影响因子：
5.5
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Li H;Luo Y;Liu P;Liu P;Hua W;Zhang Y;Zhang L;Li Z;Xing P;Zhang Y;Hong B;Yang P;Liu J
研究外泌体在脑缺血预处理（cerebral-IPC）对脑I/R损伤的保护作用中的作用。如前所述建立小鼠脑-IPC和MCAO/R模型，并分析它们的行为、病理和蛋白质组变化。接受 OGD/R 治疗的 Neuro-2a 使用从假手术小鼠和脑 IPC 小鼠血浆中分离的外泌体进行处理。通过 miRNA 阵列鉴定来自假手术（S-外泌体）和预处理（IPC-外泌体）小鼠的外泌体之间差异表达的 miRNA，并通过数据库搜索确定其靶标。用 IPC-外泌体、miRNA 模拟物或靶蛋白抑制剂处理对照和 OGD/R 细胞，并测量它们的活力、氧化、应激和凋亡率。通过分析相关蛋白质的水平来识别激活的途径。脑-IPC减轻了缺血和再灌注后的脑损伤，并增加了血浆外泌体的数量。 IPC-外泌体增加了 OGD/R 后 Neuro-2a 细胞的存活率。相对于 S-外泌体，IPC-外泌体中靶向 Rac1 的 miR-451a 上调。 miR-451a 模拟物和 Rac1 抑制剂 NSC23766 逆转了 OGD/R 介导的 Rac1 及其下游通路的激活。 Cerebral-IPC 通过诱导含有 miR-451a 的外泌体释放来改善脑 I/R 损伤。延迟 CIPC 对脑 I/R 损伤的保护作用的机制。
To study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral‐IPC) against cerebral I/R injury. Mouse models of cerebral‐IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro‐2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham‐operated and cerebral‐IPC mice. The differentially expressed miRNAs between exosomes derived from sham‐operated (S‐exosomes) and preconditioned (IPC‐exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC‐exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins. Cerebral‐IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC‐exosomes increased the survival of Neuro‐2a cells after OGD/R. The miR‐451a targeting Rac1 was upregulated in the IPC‐exosomes relative to S‐exosomes. The miR‐451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R‐mediated activation of Rac1 and its downstream pathways. Cerebral‐IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR‐451a. Mechanisms underlying the protective effects of delayed CIPC against cerebral I/R injury.
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