miR-874-3p Alleviates Macrophage-Mediated Inflammatory Injury in Intracerebral Hemorrhage by Targeting HIPK2.

Macrophages mediate secondary inflammatory injury after intracerebral hemorrhage (ICH). This study aimed to investigate the role and molecular mechanisms of miR-874-3p in macrophage polarization. A mice model of ICH was constructed by autologous blood injection. Macrophages were treated with erythrocyte lysates to construct an ICH cell model. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to detect miR-874-3p levels. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect macrophage polarization markers. Brain tissue water content and neurological deficit scores were used to assess the degree of inflammatory injury in ICH mice. RNA immunoprecipitation (RIP) and Dual-luciferase reporter (DLR) assays were used to analyze the targeting relationship between miR-874-3p and target mRNA. miR-874-3p levels were decreased in ICH mice and erythrocyte lysates-treated macrophages. miR-874-3p mimic alleviated inflammatory injury, decreased the levels of M1 macrophage markers, and increased the levels of M2 macrophage markers, suggesting that miR-874-3p is involved in ICH by regulating macrophage polarization. HIPK2 is the target mRNA of miR-874-3p and has the opposite expression pattern of miR-874-3p. Overexpression of HIPK2 attenuates the effect of elevated miR-874-3p levels on macrophage polarization and inflammatory brain injury in ICH mice. miR-874-3p regulates macrophage polarization in ICH by targeting HIPK2. Therefore, the miR-874-3p/HIPK2 axis may be a promising target for ICH treatment.