Neuregulin receptor degradation protein 1 (Nrdp1) is a ring finger E3 ubiquitin ligase involved in some inflammation through ubiquitination, including macrophage polarization following cerebral hemorrhage. However, there is limited understanding regarding the mechanisms through which Nrdp1 modulates macrophage polarization and the potential impact of this modulation on neurological function. Using stereotactic injection and adenoviral transfection techniques, the corresponding animal models were constructed through injecting adenovirus, saline, or blood into the mouse striatum at different periods of time in this research. The alteration in the ratio of various M1/M2 phenotype-associated markers (e.g., CD86, CD206, IL-6, IL-10, etc.) was evaluated through immunohistochemistry, immunofluorescence, western blotting, and elisa assays. Additionally, neurological function scores and behavioral tests were utilized to evaluate changes in neurological function in mice after cerebral hemorrhage. Our results show that overexpression of Nrdp1 promotes the expression of a variety of M2 macrophage-associated markers and enhance transcriptional activity of arginase-1 (Arg1) protein through ubiquitination for early regulation M2 macrophage polarization. Additionally, Nrdp1 promotes hematoma absorption, increases IL-10 expression, inhibits inducible nitric oxide synthase (iNOS), IL-6, and TNF-α production, alleviates neurological impairment and brain edema, and accelerates functional recovery. These findings suggest that modulating macrophage polarization through Nrdp1 could be a therapeutic strategy for neurofunctional impairment in cerebral hemorrhage.

中文翻译：

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Nrdp1介导的巨噬细胞表型调节促进脑出血后轻度神经损伤小鼠的功能恢复

神经调节蛋白受体降解蛋白 1 (Nrdp1) 是一种环指 E3 泛素连接酶，通过泛素化参与某些炎症，包括脑出血后的巨噬细胞极化。然而，对于 Nrdp1 调节巨噬细胞极化的机制以及这种调节对神经功能的潜在影响的了解有限。本研究采用立体定向注射和腺病毒转染技术，通过在不同时间段向小鼠纹状体注射腺病毒、生理盐水或血液来构建相应的动物模型。通过免疫组织化学、免疫荧光、蛋白质印迹和酶联免疫吸附测定来评估各种M1/M2表型相关标志物（例如CD86、CD206、IL-6、IL-10等）的比率的变化。此外，还利用神经功能评分和行为测试来评估脑出血后小鼠神经功能的变化。我们的结果表明，Nrdp1 的过表达可促进多种 M2 巨噬细胞相关标记物的表达，并通过泛素化增强精氨酸酶 1 (Arg1) 蛋白的转录活性，从而早期调节 M2 巨噬细胞极化。此外，Nrdp1 促进血肿吸收，增加 IL-10 表达，抑制诱导型一氧化氮合酶 (iNOS)、IL-6 和 TNF-α 产生，减轻神经损伤和脑水肿，加速功能恢复。这些发现表明，通过 Nrdp1 调节巨噬细胞极化可能是脑出血神经功能损伤的一种治疗策略。