| 引用本文: | 杨淑颖,潘娜,张璟,刘梦婷,宋海波.ZJU-37在多发性硬化脱髓鞘模型中的神经保护作用研究[J].中国临床新医学,,():-. |
| Yang Shuying.ZJU-37在多发性硬化脱髓鞘模型中的神经保护作用研究[J].中国临床新医学,,():-. |
|
| 摘要: |
| 目的：探讨受体相互作用蛋白激酶1（RIPK1）新型抑制剂ZJU-37对实验性多发性硬化症（MS）小鼠模型的神经保护作用。方法：本研究首先从GEO数据库获取GSE172497数据集，利用R语言分析了少突胶质前体细胞（OPC）中ZJU-37处理组与对照组的差异表达基因并进行通路富集分析。在动物实验中，采用Cuprizone饲料诱导建立MS小鼠模型，并将小鼠随机分为三组：Control组（标准饲料）、Cuprizone模型组（0.2% Cuprizone饲料+溶剂腹腔注射）及ZJU-37干预组（Cuprizone饲料+10 mg/kg ZJU-37腹腔注射）。干预6周后，取脑组织进行免疫荧光、髓鞘染色和透射电镜观察，分别评估OPC增殖情况、髓鞘脱失程度和超微结构变化，同时通过免疫组化与Western blot检测p-RIPK1蛋白的表达水平。结果：生信分析提示ZJU-37可调控OPC中细胞周期及DNA修复相关信号通路。动物实验表明，与Cuprizone模型组相比，ZJU-37干预能够促进OPC增殖（P < 0.0001），减少胼胝体脱髓鞘面积，改善髓鞘超微结构（P < 0.001），提高有髓轴突比例并维持髓鞘厚度（P < 0.0001），同时显著降低p-RIPK1的阳性细胞数（P < 0.0001）与蛋白表达水平。结论：ZJU-37能够下调MS小鼠脑组织中p RIPK1的表达，减轻髓鞘损伤并增强神经保护作用，该效应可能与其促进少突胶质前体细胞（OPC）增殖有关。 |
| 关键词: 多发性硬化症 髓鞘 ZJU-37 神经保护 受体相互作用蛋白激酶1 |
| DOI： |
| 分类号: |
| 基金项目:山东省自然科学基金；山东省中医药科技项目 |
|
| Study of neuroprotective effect of ZJU-37 in a Multiple Sclerosis Demyelination Model |
|
Yang Shuying
|
|
Zibo Maternal and Child Health Hospital
|
| Abstract: |
| Objective: To investigate the neuroprotective effect of ZJU-37, a novel Receptor-interacting protein kinase 1 (RIPK1) inhibitor, in an experimental mouse model of multiple sclerosis (MS). Methods: The dataset GSE172497 was obtained from the GEO database, and differential expression analysis along with pathway enrichment analysis between the ZJU-37 treatment group and the control group in oligodendrocyte precursor cells (OPCs) were performed using R. For the animal study, an MS mouse model was established by Cuprizone induction. Mice were randomly divided into three groups: the Control group (standard diet), the Cuprizone model group (0.2% Cuprizone diet + daily solvent injection), and the ZJU-37 intervention group (Cuprizone diet + daily intraperitoneal injection of ZJU-37 at 10 mg/kg). After 6 weeks of intervention, brain tissues were collected. Immunofluorescence，Myelin staining and transmission electron microscopy (TEM) were used to evaluate the OPC proliferation，degree of demyelination and ultrastructural changes, respectively. Immunohistochemistry and Western blot were performed to detect the expression level of p-RIPK1 protein. Results:?Bioinformatics analysis suggested that ZJU-37 could regulate signaling pathways related to the cell cycle and DNA repair in OPCs. Animal experiments showed that compared with the Cuprizone model group, ZJU-37 intervention significantly promotes OPC proliferation (P < 0.001) and reduced the area of demyelination in the corpus callosum, improved myelin ultrastructure (P < 0.001), increased the proportion of myelinated axons and maintained myelin thickness (P < 0.0001), while markedly decreasing the number of p-RIPK1-positive cells (P < 0.0001) and the protein expression level of p-RIPK1. Conclusion:?ZJU-37 can down-regulate the expression of p-RIPK1 in the brain tissue of MS mice, alleviate myelin damage, and enhance neuroprotection. This effect may be related to its promotion of oligodendrocyte precursor cell (OPC) proliferation. |
| Key words: Multiple sclerosis Myelin ZJU?37 Neuroprotection Receptor?interacting protein kinase 1 |
