通过生物信息学方法预测慢性脑低灌注的免疫治疗靶点  

Prediction of immunotherapy targets for chronic cerebral hypoperfusion by bioinformatics method

作　　者：赵梅[1] 薛艳鹏 田青青 杨赫 蒋晴 于孟凡 陈鑫[2,3,4] ZHAO Mei;XUE Yanpeng;TIAN Qingqing;YANG He;JIANG Qing;YU Mengfan;CHEN Xin(Department of Pharmacy,Sanya Central Hospital(The Third People's Hospital of Hainan Province),Sanya,Hainan 572000,P.R.China;Department of Neurosurgery,First Affiliated Hospital of Harbin Medical University,Harbin 150001,P.R.China;Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province,Harbin 150001,P.R.China;Institute of Neuroscience,Sino-Russian Medical Research Center,Harbin Medical University,Harbin 150001,P.R.China)

机构地区：[1]三亚中心医院(海南省第三人民医院)药学部,海南三亚572000 [2]哈尔滨医科大学第一附属医院神经外科,哈尔滨150001 [3]黑龙江省普通高校神经外科重点实验室,哈尔滨150001 [4]哈尔滨医科大学中俄医学研究中心神经科学研究所,哈尔滨150001

出　　处：《生物医学工程学杂志》2025年第2期382-388,395,共8页Journal of Biomedical Engineering

基　　金：海南省自然科学基金(高层次人项目)(822RC872)。

摘　　要：慢性脑低灌注(CCH)在血管性痴呆(VD)的发生和发展中起着重要作用。近年来的研究表明,脑缺血过程中涉及多阶段的免疫炎症反应,因而脑缺血的免疫治疗逐渐受到关注。本研究旨在通过生物信息学方法,从免疫学的视角确定CCH的潜在免疫治疗靶点。我们共鉴定出823个与CCH相关的差异基因,并筛选出9个与免疫功能相关的核心基因,分别是RASGRP1、FGF12、SEMA7A、PAK6、EDN3、BPHL、FCGRT、HSPA1B和MLNR。基因富集分析显示,这些核心基因主要参与细胞生长、神经投射延伸及间充质干细胞迁移等生物学功能。生物信号通路分析表明,核心基因主要参与T细胞受体、Ras及MAPK等信号通路的调控。通过LASSO回归,我们进一步筛选出RASGRP1和BPHL作为关键的免疫相关核心基因。同时,结合差异miRNA及miRwalk数据库,我们确定miR-216b-5p为调控RASGRP1的关键免疫相关miRNA。综上所述,本研究预测的miR-216b-5p/RASGRP1信号通路在CCH的免疫调节中具有重要意义,有望为CCH的免疫治疗提供新的靶点。Chronic cerebral hypoperfusion(CCH) plays an important role in the occurrence and development of vascular dementia(VD). Recent studies have indicated that multiple stages of immune-inflammatory response are involved in the process of cerebral ischemia, drawing increasing attention to immune therapies for cerebral ischemia. This study aims to identify potential immune therapeutic targets for CCH using bioinformatics methods from an immunological perspective. We identified a total of 823 differentially expressed genes associated with CCH, and further screened for 9 core immune-related genes, namely RASGRP1, FGF12, SEMA7A, PAK6, EDN3, BPHL, FCGRT, HSPA1B and MLNR. Gene enrichment analysis showed that core genes were mainly involved in biological functions such as cell growth, neural projection extension, and mesenchymal stem cell migration. Biological signaling pathway analysis indicated that core genes were mainly involved in the regulation of T cell receptor, Ras and MAPK signaling pathways.Through LASSO regression, we identified RASGRP1 and BPHL as key immune-related core genes. Additionally, by integrating differential miRNAs and the miRwalk database, we identified miR-216b-5p as a key immune-related miRNA that regulates RASGRP1. In summary, the predicted miR-216b-5p/RASGRP1 signaling pathway plays a significant role in immune regulation during CCH, which may provide new targets for immune therapy in CCH.

关 键 词：慢性脑低灌注 免疫治疗 生物信息学 

分 类 号：R743[医药卫生—神经病学与精神病学]