CD36-Mediated Hematoma Absorption following Intracerebral Hemorrhage: Negative Regulation by TLR4 Signaling
CD36-Mediated Hematoma Absorption following Intracerebral Hemorrhage: Negative Regulation by TLR4 Signaling
复制标题
脑出血后 CD36 介导的血肿吸收：TLR4 信号传导的负调控
DOI：
10.4049/jimmunol.1400054
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发表时间：
2014-06-15
影响因子：
4.4
通讯作者：
Yang, QingWu
中科院分区：
文献类型：
--
作者：
Fang, Huang;Chen, Jing;Yang, QingWu
促进血肿吸收是治疗脑出血的一种新策略，但血肿吸收的机制尚不清楚。本研究利用体外和体内脑出血模型，探讨CD36在血肿吸收中的作用及其可能机制。对CD36缺陷的脑出血患者进行血肿吸收检查。与CD36表达正常的患者相比，CD36表达缺陷的脑出血患者血肿吸收减慢，神经功能缺失加重。野生型小鼠脑出血后血肿周围组织中CD36的表达增加，而−/−小鼠的血肿吸收减少。−/−小鼠神经功能缺失加重，肿瘤坏死因子-α和IL-1β表达水平升高。CD36−/−小胶质细胞对红细胞的吞噬能力也降低。此外，TLR4−/−和MyD88−/−小鼠脑出血后血肿周围CD36的表达显著增加，血肿吸收明显增加，而抗CD36单抗可显著抑制这一作用。在体外，肿瘤坏死因子-α和IL-1β可显著抑制小胶质细胞CD36的表达，降低红细胞对小胶质细胞的吞噬能力。TLR4抑制剂TAK-242上调小胶质细胞CD36表达，促进血肿吸收，增加过氧化氢酶表达，降低H_2O_2含量。提示CD36介导了脑出血后血肿的吸收，TLR4信号通路抑制了CD36的表达，从而减缓了血肿的吸收。抑制TLR4可促进血肿吸收，明显改善脑出血后神经功能障碍。
Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic deficits. CD36 expression in perihematomal tissues in wild-type mice following ICH was increased, whereas the hematoma absorption in CD36−/− mice was decreased. CD36−/− mice also showed aggravated neurologic deficits and increased TNF-α and IL-1β expression levels. The phagocytic capacity of CD36−/− microglia for RBCs was also decreased. Additionally, the CD36 expression in the perihematoma area after ICH in TLR4−/− and MyD88−/− mice was significantly increased, and hematoma absorption was significantly promoted, which was significantly inhibited by an anti-CD36 Ab. In vitro, TNF-α and IL-1β significantly inhibited the microglia expression of CD36 and reduced the microglia phagocytosis of RBCs. Finally, the TLR4 inhibitor TAK-242 upregulated CD36 expression in microglia, promoted hematoma absorption, increased catalase expression, and decreased the H2O2 content. These results suggested that CD36 mediated hematoma absorption after ICH, and TLR4 signaling inhibited CD36 expression to slow hematoma absorption. TLR4 inhibition could promote hematoma absorption and significantly improve neurologic deficits following ICH.