Yu Miao, Tian Tian, Zhang Jiwei, Hu Tiemin
Department of Neurosurgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
Department of Neurosurgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
J Clin Neurosci. 2022 May;99:253-260. doi: 10.1016/j.jocn.2022.03.010. Epub 2022 Mar 17.
MicroRNAs (miRNAs) participate in the diagnosis and treatment of intracerebral hemorrhage (ICH). miR-141-3p has been widely reported to regulate neurological disorders and cerebropathy. However, the specific role of miR-141-3p in ICH has not yet been revealed. The aim of this study was exploration of the biological functions and mechanism of miR-141-3p in ICH by establishing a collagenase-induced ICH mouse model. After ICH induction, miR-141-3p mimics or miR-NC were administered into the right striatum of the model mice followed by the performance of neurological tests. After euthanasia of the mice, the injury volume, brain water content, and injury to the blood-brain barrier (BBB) were evaluated. Evans blue (EB) was used to stain the brain slices, and EB extravasation was detected to evaluate the injury to BBB. miR-141-3p expression in perihematomal edema and hematoma areas after ICH was assessed by RT-qPCR. The levels of tight junction proteins in brain tissues and human brain microvascular endothelial cells (BMECs) were evaluated by western blotting. The FITC-dextran 20 method was used to assess BMEC permeability. The binding between miR-141-3p and zinc finger E-box-binding homeobox 2 (ZEB2) was verified with a luciferase reporter assay. In this study, miR-141-3p overexpression alleviated ICH-induced brain injury and protected BBB integrity in vivo. ZEB2 was a target gene of miR-141-3p. ZEB2 overexpression promoted BBB disruption, and miR-141-3p overexpression attenuated the promoting effect exerted by ZEB2. Overall, miR-141-3p protects against BBB disruption and attenuates brain injuries induced by ICH by targeting ZEB2.
微小RNA（miRNA）参与脑出血（ICH）的诊断和治疗。miR-141-3p已被广泛报道可调节神经紊乱和脑部疾病。然而，miR-141-3p在ICH中的具体作用尚未明确。本研究的目的是通过建立胶原酶诱导的ICH小鼠模型，探索miR-141-3p在ICH中的生物学功能及机制。ICH诱导后，将miR-141-3p模拟物或miR-NC注入模型小鼠的右侧纹状体，随后进行神经功能测试。对小鼠实施安乐死后，评估损伤体积、脑含水量及血脑屏障（BBB）损伤情况。采用伊文思蓝（EB）对脑切片进行染色，检测EB外渗以评估BBB损伤。通过RT-qPCR评估ICH后血肿周围水肿和血肿区域的miR-141-3p表达。采用蛋白质免疫印迹法评估脑组织和人脑微血管内皮细胞（BMEC）中紧密连接蛋白的水平。采用FITC-葡聚糖20法评估BMEC通透性。通过荧光素酶报告基因检测验证miR-141-3p与锌指E盒结合同源框2（ZEB2）之间的结合。在本研究中，miR-141-3p过表达减轻了ICH诱导的脑损伤，并在体内保护了BBB的完整性。ZEB2是miR-141-3p的靶基因。ZEB2过表达促进BBB破坏，而miR-141-3p过表达减弱了ZEB2发挥的促进作用。总体而言，miR-141-3p通过靶向ZEB2保护BBB免受破坏，并减轻ICH诱导的脑损伤。
