中文摘要：

髓鞘再生障礙是多發(fā)性硬化等脫髓鞘疾病呈進行性加重的根本原因。目前學(xué)界尚不明確這類疾病中內(nèi)源性修復(fù)機制頻繁失效的具體機制?，F(xiàn)有研究證據(jù)表明，該現(xiàn)象與兩大因素相關(guān)：一是病灶微環(huán)境過度炎癥化，二是少突膠質(zhì)前體細胞（OPC）自身存在分化缺陷，無法發(fā)育為成熟髓鞘形成細胞。

本團隊前期研究發(fā)現(xiàn)，蘋果、草莓中含量豐富的黃酮類化合物根皮素可誘導(dǎo)巨噬細胞向抗炎表型極化，進而減輕神經(jīng)炎癥。本研究證實，根皮素在離體組織模型與在體動物模型中均能顯著促進髓鞘再生。根皮素促髓鞘再生作用不依賴小膠質(zhì)細胞功能與炎癥水平的改變，而是直接作用于少突膠質(zhì)前體細胞，加速其成熟。機制層面，根皮素可作為脂肪酸感應(yīng)核受體過氧化物酶體增殖物激活受體 γ（PPARγ）的直接配體，進而推動少突膠質(zhì)前體細胞成熟。

綜上，本研究證實根皮素具備促進中樞神經(jīng)系統(tǒng)損傷修復(fù)的活性，為開發(fā)靶向髓鞘再生的治療藥物、膳食干預(yù)方案提供了廣闊新思路。

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.

論文信息：

論文題目：Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation

期刊名稱：PNAS

時間期卷：119 (46) e2120393119

DOI: 10.1073/pnas.212039311

產(chǎn)品信息：

貨號：C-010

規(guī)格：10ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體體外培養(yǎng)清除小膠質(zhì)細胞模型里巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS：根皮素通過刺激少突膠質(zhì)細胞前體細胞分化來增強髓鞘再生。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細胞的材料和方法：

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.

巨噬細胞清除材料和方法文獻截圖：