脑动脉瘤破裂出血后脑脊液中miRNA-3177-3p与脑血管痉挛的发病关系及临床意义
作者:
作者单位:

1.安徽医科大学第一附属医院神经外科,安徽 合肥 230041;2.安徽省公共卫生临床中心神经外科,安徽 合肥 230041;3.安徽省转化医学研究院,安徽 合肥 230031;4.安徽医科大学第二附属医院神经外科,安徽 合肥 230031

作者简介:

翁传波(1988—),男,神经外科主治医师,硕士学位,主要从事神经外科基础与临床相关研究,Email: rehomail@163.com。

通信作者:

江涛(1976—),男,神经外科主任医师,博士学位,主要从事神经外科(特别是脑血管病)基础与临床相关研究,Email: jiangtao_aysfy@163.com。

基金项目:

安徽医科大学校科研基金项目(2019xkj067);安徽省转化医学研究院科研基金项目(2021zhyx-C72)。


Association of miRNA-3177-3p in cerebrospinal fluid with cerebral vasospasm after aneurysmal subarachnoid hemorrhage and its clinical significance
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Affiliation:

1.Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230041, China;2.Department of Neurosurgery, Anhui Public Health Clinical Center, Hefei, Anhui 230041, China;3.Anhui Provincial Institute of Translational Medicine, Hefei, Anhui 230031, China;4.Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China

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    摘要:

    目的 测定动脉瘤性蛛网膜下腔出血(aSAH)后脑血管痉挛(CV)患者与脑血管未痉挛患者脑脊液中miRNA-3177-3p的表达情况,探讨其与CV的发病关系及临床意义。方法 将29例aSAH患者分成脑血管痉挛组(CV组)与脑血管未痉挛组(non-CV组)。比较两组患者的一般临床资料;通过生物信息数据分析确定miRNA-3177-3p作为研究对象,测定两组患者脑脊液中miRNA-3177-3p实际表达情况并比较差异;预测miRNA-3177-3p下游靶基因ATP1B3,构建ATP1B3质粒,双萤光素酶报告实验验证miRNA-3177-3p与ATP1B3靶向关系;最后,ELISA法测定两组患者脑脊液中ATP1B3转录产物ATP1β3含量并比较差异。结果 CV组患者Hunt评级高于non-CV组(P<0.05);CV组脑脊液中miRNA-3177-3p表达丰度为(0.873±0.044),与non-CV组(0.908±0.034)比较,差异有统计学意义(t=2.157,P=0.040);双萤光素酶报告实验结果显示,与miRNA-3177-3p作用后,ATP1B3-3′UTR区相较对照组活性降低15%(P<0.05);将ATP1B3-3′UTR区进行突变,ATP1B3-3′UTR区相较突变前活性上升14%(P<0.05);ELISA法证实表达产物ATP1β3在CV组脑脊液中(1.776±0.013)ng/mL高于non-CV组(1.722±0.016)ng/mL(t=7.778,P=0.000)。结论 CV患者脑脊液中miRNA-3177-3p表达下调,ATP1B3高表达可能参与了CV的发病过程,该机制可能在预测与治疗CV上具有一定临床意义。 [国际神经病学神经外科学杂志, 2023, 50(3): 6-11]

    Abstract:

    Objective To investigate the association of miRNA-3177-3p with cerebral vasospasm (CV) and its clinical significance by measuring the expression of miRNA-3177-3p in cerebrospinal fluid (CSF) in patients with or without CV after aneurysmal subarachnoid hemorrhage (aSAH).Methods A total of 29 aSAH patients were divided into CV group and non-CV group. General clinical data were compared between the two groups; miRNA-3177-3p was determined as the target miRNA after integrated bioinformatics analysis, and the expression of miRNA-3177-3p in CSF was measured and compared between the two groups; after ATP1B3 was predicted as the downstream target gene of miRNA-3177-3p, ATP1B3 plasmids were constructed and the dual-luciferase reporter gene assay was used to verify the targeting relationship between miRNA-3177-3p and ATP1B3; finally, ELISA was used to measure the content of ATP1β3, a transcription product of ATP1B3, in CSF, which was then compared between the two groups.Results The CV group had a significantly higher Hunt grade than the non-CV group (P <0.05). There was a significant difference in the expression level of miRNA-3177-3p in CSF between the CV group and the non-CV group (0.873±0.044 vs 0.908±0.034, t = 2.157, P = 0.040). The dual-luciferase reporter gene assay showed that after interaction with miRNA-3177-3p, the activity of ATP1B3-3′UTR region was reduced by 15% compared with the control group (P <0.05), while the activity of ATP1B3-3′UTR region was increased by 14% after mutation (P <0.05). ELISA showed that the CV group had a significantly higher level of ATP1β3 in CSF than the non-CV group (1.776±0.013 ng/mL vs 1.722±0.016 ng/mL, t = 7.778, P = 0.000).Conclusion The expression level of miRNA-3177-3p is downregulated in CV patients, and the high expression of its target gene ATP1B3 may be involved in the pathogenesis of CV. This mechanism may have a certain clinical significance in the prediction and treatment of CV. [Journal of International Neurology and Neurosurgery, 2023, 50(3): 6-11]

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翁传波,江涛,张洋,刘师林,江录伟,王绪扣456.脑动脉瘤破裂出血后脑脊液中miRNA-3177-3p与脑血管痉挛的发病关系及临床意义[J].国际神经病学神经外科学杂志,2023,50(3):6-11111WENG Chuanbo, JIANG Tao, ZHANG Yang, LIU Shilin, JIANG Luwei, WANG Xukou222. Association of miRNA-3177-3p in cerebrospinal fluid with cerebral vasospasm after aneurysmal subarachnoid hemorrhage and its clinical significance[J]. Journal of International Neurology and Neurosurgery,2023,50(3):6-11

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  • 收稿日期:2022-05-17
  • 最后修改日期:2023-03-23
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  • 在线发布日期: 2023-08-16
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