中文摘要：
髓鞘再生障碍是多发性硬化等脱髓鞘疾病呈进行性加重的根本原因。目前学界尚不明确这类疾病中内源性修复机制频繁失效的具体机制。现有研究证据表明，该现象与两大因素相关：一是病灶微环境过度炎症化，二是少突胶质前体细胞（OPC）自身存在分化缺陷，无法发育为成熟髓鞘形成细胞。
本团队前期研究发现，苹果、草莓中含量丰富的黄酮类化合物根皮素可诱导巨噬细胞向抗炎表型极化，进而减轻神经炎症。本研究证实，根皮素在离体组织模型与在体动物模型中均能显著促进髓鞘再生。根皮素促髓鞘再生作用不依赖小胶质细胞功能与炎症水平的改变，而是直接作用于少突胶质前体细胞，加速其成熟。机制层面，根皮素可作为脂肪酸感应核受体过氧化物酶体增殖物激活受体 γ（PPARγ）的直接配体，进而推动少突胶质前体细胞成熟。
综上，本研究证实根皮素具备促进中枢神经系统损伤修复的活性，为开发靶向髓鞘再生的治疗药物、膳食干预方案提供了广阔新思路。
英文摘要：
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries, reduces neuroinflammation by driving macrophages toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination.
论文信息：
论文题目：Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation
期刊名称：PNAS
时间期卷：119 (46) e2120393119
DOI: 10.1073/pnas.212039311
产品信息：
货号：C-010
规格：10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体体外培养清除小胶质细胞模型里巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS：根皮素通过刺激少突胶质细胞前体细胞分化来增强髓鞘再生。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
Cerebellar slices were obtained from C57BL/6JOlaHsd mouse pups at the age of P9 or P10, as described previously (31, 32). To induce demyelination, slices were treated with lysolecithin (LPC; 0.5 mg/mL; Sigma-Aldrich) 3 d after isolation for 16 h. After demyelination, slices were treated daily with phloretin (50 μM) or vehicle for 6 d. For microglia depletion, slices were treated with clodronate or empty liposomes (0.5 mg/mL; LIPOSOMA) immediately after isolation for 24 h. After 3 d, slices were treated with LPC for 16 h followed by daily treatment with phloretin or vehicle.
巨噬细胞清除材料和方法文献截图：
