Heme Oxygenase-1 may Mediate Early Inflammatory Response of Intracerebral Hemorrhage through Toll-like Receptor 4 Signaling Pathway
Heme Oxygenase-1 may Mediate Early Inflammatory Response of Intracerebral Hemorrhage through Toll-like Receptor 4 Signaling Pathway
复制标题
Hemeoxygenase-1可能通过Toll样受体4信号通路介导脑出血早期炎症反应。
DOI：
10.2174/1567202619666220614153209
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发表时间：
2022-01-01
影响因子：
2.1
通讯作者：
Qi, Jiping
中科院分区：
文献类型：
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作者：
Song, Yuejia;Li, Ke;Qi, Jiping
目的：探讨血红素氧合酶-1(HO-1)是否通过调节Toll样受体4(TLR4)信号通路促进脑出血(ICH)后早期神经炎性反应。我们将受试者分为对照组、脑出血组和脑出血加锌原卟啉IX(ZnPP)组。免疫荧光和免疫印迹法检测脑出血后HO-1和TLR4的时间表达模式和细胞定位；抑制HO-1的表达后，采用免疫印迹法检测TLR4蛋白、下游分子髓系分化因子88(MyD88)、Toll和白介素1受体(TIR)结构域适配子诱导的干扰素-β(TRIF)以及炎症因子的表达水平。结果：免疫荧光显示HO-1和TLR4在脑出血后具有相似的时间表达模式和细胞定位，抑制HO-1可减少TLR4蛋白途径的表达，包括TLR4、MyD88、TRIF和相关炎症因子。结论：HO-1可能通过TLR4/MyD88/TRIF信号通路促进脑出血后早期神经炎症的发生。
Objective: The aim of this study was to investigate whether heme oxygenase-1 (HO-1) promotes an early neuroinflammatory response after intracerebral hemorrhage (ICH) by regulating the toll-like receptor 4 (TLR4) signaling pathway.Methods: We used a stereotaxic instrument to induce a mouse model of ICH through collagenase. We divided the participants into a control group, an ICH group, and an ICH and zinc protoporphyrin IX (ZnPP) group. The temporal expression pattern and cell localization of HO-1 and TLR4 after the ICH were detected by immunofluorescence and western blot; after the expression of HO-1 was inhibited, the expression levels of the TLR4 protein, the downstream molecule myeloid differentiation factor 88 (MyD88), the Toll and interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-beta (TRIF) and the inflammatory factors were measured by western blotting.Results: Immunofluorescence showed that HO-1 and TLR4 had similar temporal expression patterns and cellular localization after ICH, and we found that inhibiting HO-1 reduces the expression of TLR4 protein pathways, including TLR4, MyD88, TRIF, and related inflammatory factors, by studying the inhibitor ZnPP.Conclusion: These results indicate that HO-1 may promote early neuroinflammation after ICH through the TLR4/MyD88/TRIF signaling pathway.