MicroRNA-23b alleviates neuroinflammation and brain injury in intracerebral hemorrhage by targeting inositol polyphosphate multikinase
MicroRNA-23b alleviates neuroinflammation and brain injury in intracerebral hemorrhage by targeting inositol polyphosphate multikinase
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MicroRNA-23b 通过靶向肌醇多磷酸多激酶减轻脑出血中的神经炎症和脑损伤
DOI：
10.1016/j.intimp.2019.105887
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
He, Zhiyi
中科院分区：
文献类型：
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作者：
Hu, Liuting;Zhang, Heyu;He, Zhiyi
神经炎症在脑出血（ICH）的发病机制中起着关键作用，导致有害的脑损伤和神经功能缺损。microRNA-23 b（miR-23 b）在许多疾病中发挥抗炎作用，并在ICH患者中下调。本研究的目的是评估miR-23 b在体内和体外ICH模型中的参与，分别使用大鼠基底神经节注射VII型胶原酶和氯化血红素刺激细胞。通过RT-qPCR评估通过用慢病毒-miR-23 b（LV-miR-23 b）或miR-23 b模拟物转染的miR-23 b的外源性过表达。本研究发现，miR-23 b在脑出血模型中表达下调，其过表达可有效减轻脑出血大鼠的神经功能缺损、脑水肿、血肿面积和神经元凋亡。Western blotting检测神经炎症标志物和免疫荧光染色检测小胶质细胞活化，结果表明miR-23 b可减轻脑出血的神经炎症反应。我们还使用BV 2小胶质细胞和HT 22神经元细胞系进行了体外机制研究，以探索miR-23 b如何调节ICH后的神经炎症和神经元保护。我们发现miR-23 b显著降低了BV 2细胞中氯化血红素刺激的炎症反应，并减弱了共培养的HT 22神经元细胞死亡。此外，我们证实了miR-23 b通过靶向肌醇多磷酸多激酶（IPMK）抑制BV 2细胞中的炎症，并且通过Akt/mTOR途径的自噬调节参与了ICH后miR-23 b调节的炎症。我们的研究表明，miR-23 b通过靶向IPMK抑制神经炎症在ICH中发挥保护作用;该机制可能与调节Akt/mTOR自噬通路有关，使其成为ICH治疗的潜在靶点。
Neuroinflammation plays a critical role in the pathogenesis of intracerebral hemorrhage (ICH), contributing to detrimental brain injury and neurological function deficits. MicroRNA-23b (miR-23b) exerts anti-inflammatory effects in many diseases and is downregulated in patients with ICH. This study aimed to evaluate the involvement of miR-23b in ICH models in vivo and in vitro, using basal ganglia injection of collagenase type VII in rats and hemin stimulation for cells, respectively. Exogenous overexpression of miR-23b by transfection with lentivirus-miR-23b (LV-miR-23b) or miR-23b mimics was evaluated by RT-qPCR. In this study, we found miR-23b was downregulated in the ICH models and its overexpression effectively alleviated neurological deficits, brain edema, hematoma area, and neuronal apoptosis in ICH rats. Western blotting for neuroinflammation markers and immunofluorescence staining for microglial activation demonstrated that miR-23b could alleviate neuroinflammation in ICH in vivo. We also performed an in vitro mechanism study using BV2 microglial cells and HT22 neuronal cell lines to explore how miR-23b modulates neuroinflammation and neuronal protection after ICH. We found that miR-23b significantly decreased hemin-stimulated inflammation response in BV2 cells and attenuated co-cultured HT22 neuronal cell death. Additionally, we verified that miR-23b suppressed inflammation in BV2 cells by targeting inositol polyphosphate multikinase (IPMK) and that autophagy regulation through the Akt/mTOR pathway was involved in miR-23b-regulated inflammation after ICH. Our study illustrated that miR-23b played a protective role in ICH through inhibiting neuroinflammation by targeting IPMK; this mechanism may be related to the regulation of the Akt/mTOR autophagy pathway, making it a potential target for ICH treatment.