Abstract：
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.
摘要：
神经调节素受体降解蛋白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,关于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理解有限.使用立体定向注射和腺病毒转染技术，通过注射腺病毒构建相应的动物模型，盐水,在这项研究中，或血液在不同的时间段进入小鼠纹状体。各种M1/M2表型相关标志物的比率的改变(例如，CD86、CD206、IL-6、IL-10等。)通过免疫组织化学进行评估，免疫荧光，西方印迹,和elisa检测。此外,采用神经功能评分和行为学测试评价脑出血后小鼠神经功能的变化。我们的结果表明，Nrdp1的过表达促进多种M2巨噬细胞相关标志物的表达，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巨噬细胞的极化。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的产生，减轻神经功能缺损和脑水肿，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中神经功能障碍的治疗策略。
