Target significance and inflammatory response mechanisms ofpodoplanin in the treatment of cerebral haemorrhage

摘要：

通过生物信息学方法探讨了平足蛋白(podoplanin,PDPN)在实验性脑出血中的表达及其功能机制，以期为脑出血的治疗提供新的靶点和理论依据.首先，基于GSE216607数据集筛选出与脑出血相关的差异表达基因，并结合机器学习算法确定了3个核心基因:PDPN、C_dk2和C_xcl16.对这些基因进行了功能富集分析，评估其潜在的生物学通路.重点研究PDPN,构建脑出血动物模型，采用免疫印迹、qPCR、免疫组化及免疫荧光等方法验证PDPN在脑出血后小胶质细胞中的高表达，并探讨其信号通路.结果显示，PDPN在脑出血后小胶质细胞中表达显著上调，且使用 PDPN抑制性单克隆抗体SZ168治疗后显著改善了小鼠的短期神经功能损伤和血肿情况，通过NF-kB通路的调控抑制小胶质细胞向促炎表型转化，并促进其向抑炎表型转化，减少炎症因子的释放,综上,PDPN通过调节小胶质细胞极化功能，参与了脑出血后的神经炎症反应，其作为潜在靶点为脑出血治疗提供了新的思路.

In this study, we investigated the role of podoplanin (PDPN) in cerebral hemorrhage using bioinformatics and experimental approaches. Differentialy expressed genes related to cerebral hemorrhage were identilied from the GSE2166o7 dataset, and three core genes(PDPN, Cdk2, and Ccl16) were selected using machine learning algorithms. Functional enrich-ment analysis revealed their involvement in key biological pathways. Focusing on PDPN, we constructed a cerebral hemorhage animal model and verified that PDPN expression was significanty up-regulated in microglia after hemorrhage. Treatment with the PDPN-inhibitory monoclonal antibody SZ168 improved neurological deficits and reduced hematomas in mice,Mechanistical-Iy, SZ168 inhibited microglial polarization toward a pro-inflammatory phenotype and promoted an ant-inflammatory phenotype by modulating the NF-kB pathway. thereby reducing inflammatory factor release. In conclusion, PDPN plays a critical role in neuroinflammation after cerebral hemorrhage by regulating microglial polarization, suggesting its potential as a therapeutic tar get for cerebral hemorrhage treatment.

作者：

刘诗谣，赵益明

Liu Shiyao,Zhao Yiming

机构地区：

苏州大学附属第一医院国家卫生计生委止血与血栓实验室；江苏省血液研究所

引用本文：

刘诗谣,赵益明.靶向平足蛋白调控小胶质细胞极化减轻脑出血后神经炎症机制研究[J].河南师范大学学报(自然科学版),2026,54(5):134-141. (Liu Shiyao,Zhao Yiming. Target significance and inflammatory response mechanisms of podoplanin in the treatment of cerebral haemorrhage[J].Journal of Henan Normal University

(Natural Science Edition),2026,54(5):134-141.DOI:10.16366/j.cnki.1000-2367.2025.02.17.0003.)

基金：

国家自然科学基金

关键词：

脑出血;炎症反应;平足蛋白;小胶质细胞;生物信息学

cerebral haemorrhage; inflammation response; podoplanin; microglia; bioinformatics

分类号：

Q189;R543.5

靶向平足蛋白调控小胶质细胞极化减轻脑出血后神经炎症机制研究.pdf