普仑司特调控中枢病理性免疫炎症微环境改善大鼠脑缺血再灌注损伤*

doi:10.3870/j.issn.1672-0741.26.01.019

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (5): 614-623.doi: 10.3870/j.issn.1672-0741.26.01.019

普仑司特调控中枢病理性免疫炎症微环境改善大鼠脑缺血再灌注损伤^*

张添琦^1#, 王江友^1,2#, 曾巧春¹, 李交义¹, 胡智慧¹, 朱玉玲¹, 曹晓璐^1△

¹武汉科技大学医学院,职业危害识别与控制湖北省重点实验室,武汉 430065;
²武汉科技大学附属武汉亚心总医院心内科,武汉 430056

收稿日期:2026-01-12 发布日期:2026-10-30
通讯作者: ^△E-mail：caoxiaolu@wust.edu.cn
作者简介:张添琦,男,2004年生,医学本科生,E-mail：2398553466@qq.com;王江友,男,1987年生,博士研究生,E-mail：drwangjiangyou@163.com; ^#共同第一作者
基金资助:
^*国家自然科学基金资助项目（No.81801307）; 湖北省自然科学基金资助项目（No.2026AFB516）; 职业危害识别与控制湖北省重点实验室联合基金资助项目（No.JF2023-K05）

Pranlukast Attenuates Cerebral Ischemia-Reperfusion Injury in Rats by Modulating the Central Pathological Immune-Inflammatory Microenvironment

Zhang Tianqi^1#, Wang Jiangyou^1,2#, Zeng Qiaochun¹ et al

¹Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China;
²Department of Cardiology, Wuhan Asia General Hospital, Affiliated Hospital of Wuhan University of Science and Technology, Wuhan 430056, China

Received:2026-01-12 Published:2026-10-30
Contact: ^△E-mail：caoxiaolu@wust.edu.cn

摘要/Abstract

摘要： 目的揭示普仑司特（Pranlukast）通过非经典途径减轻脑缺血再灌注（CIR）损伤的潜在靶标与关键调控机制。方法采用PharmMapper反向虚拟筛选、分子模拟,结合基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集分析,进行普仑司特潜在作用靶点及调控通路筛选;采用PC12细胞构建氧糖剥夺/复氧复糖（oxygen-glucose deprivation/reperfusion, OGD/R）模型,CCK-8法评估细胞活力,PI、Hoechst 33342染色评估细胞存活率;以SD大鼠构建大脑中动脉闭塞/再灌注（middle cerebral artery occlusion/reperfusion, MCAO/R）模型,通过神经功能评分、TTC、苏木精-伊红染色进行整体药效评估,通过检测MPO、iNOS/CD206免疫荧光、p-p65、IL-6免疫组化及髓鞘透射电镜进行调控机制验证。结果确定SRC、MAPK14、ADAM17为普仑司特抗CIR损伤的高亲和力靶点,并通过调控MAPK、PI3K-Akt等信号通路介导的免疫-炎症相互作用网络发挥作用。体内、外实验表明,普仑司特能显著提高OGD/R细胞活力与存活率;改善MCAO/R大鼠神经功能损伤,缩小脑梗死体积,减轻神经元损伤,同时可抑制中性粒细胞浸润,促进巨噬细胞M1/M2表型转换,下调p-p65及IL-6的表达,改善髓鞘结构性损伤。结论普仑司特通过调控CIR后异常的免疫-炎症相互作用,减轻免疫细胞浸润与神经炎症级联反应,保护髓鞘完整性,从而发挥抗CIR损伤的作用。

关键词: 普仑司特, 脑缺血再灌注损伤, 免疫炎症微环境, 反向虚拟筛选

Abstract: Objective To identify the potential targets and key regulatory mechanisms underlying the neuroprotective effects of Pranlukast against cerebral ischemia-reperfusion （CIR） injury. Methods PharmMapper reverse virtual screening and molecular simulation were integrated with Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses to pinpoint the potential targets and regulatory pathways of Pranlukast. An oxygen-glucose deprivation/reperfusion （OGD/R） model was established in PC12 cells; cell viability was evaluated by the CCK-8 assay, and cell survival was assessed via PI and Hoechst 33342 double staining. A middle cerebral artery occlusion/reperfusion （MCAO/R） model was constructed in SD rats; the neuroprotective effects were evaluated by neurological deficit scores, TTC staining, and HE staining. Mechanistic validation was performed by using immunofluorescence staining for MPO, iNOS, and CD206; immunohistochemical staining for p-p65 and IL-6; and transmission electron microscopy （TEM） to observe myelin sheath structure. Results SRC, MAPK14, and ADAM17 were identified as high-affinity targets through which Pranlukast attenuates CIR injury, primarily by regulating the immune-inflammatory crosstalk network involving MAPK, PI3K-Akt, and other signaling pathways. In vitro and in vivo experiments demonstrated that Pranlukast significantly enhanced the viability of OGD/R-induced PC12 cells, ameliorated neurological deficits, reduced cerebral infarct volume, and attenuated neuronal damage in MCAO/R rats. Additionally, Pranlukast inhibited neutrophil infiltration, promoted M1 to M2 phenotypic switching of macrophages, downregulated p-p65 and IL-6 expression, and ameliorated myelin sheath structural damage. Conclusion Pranlukast attenuates CIR injury by modulating aberrant immune-inflammatory crosstalk, suppressing immune cell infiltration and neuroinflammatory cascades, and preserving myelin sheath integrity.

Key words: Pranlukast, cerebral ischemia-reperfusion injury, immune-inflammatory microenvironment, reverse virtual screening

中图分类号:

R743.31

张添琦, 王江友, 曾巧春, 李交义, 胡智慧, 朱玉玲, 曹晓璐. 普仑司特调控中枢病理性免疫炎症微环境改善大鼠脑缺血再灌注损伤^*[J]. 华中科技大学学报（医学版）, 2026, 55(5): 614-623.

Zhang Tianqi, Wang Jiangyou, Zeng Qiaochun et al. Pranlukast Attenuates Cerebral Ischemia-Reperfusion Injury in Rats by Modulating the Central Pathological Immune-Inflammatory Microenvironment[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(5): 614-623.

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普仑司特调控中枢病理性免疫炎症微环境改善大鼠脑缺血再灌注损伤^*

Pranlukast Attenuates Cerebral Ischemia-Reperfusion Injury in Rats by Modulating the Central Pathological Immune-Inflammatory Microenvironment

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