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

doi:10.3870/j.issn.1672-0741.26.01.019

Abstract

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

CLC Number:

R743.31

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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