Dihydroartemisinin protects blood-brain barrier permeability during sepsis by inhibiting the transcription factor SNAI1.

Dihydroartemisinin protects blood-brain barrier permeability during sepsis by inhibiting the transcription factor SNAI1.
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双氢青蒿素通过抑制转录因子 SNAI1 来保护脓毒症期间的血脑屏障通透性

DOI:
10.1111/1440-1681.13683
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发表时间:
2022-09
影响因子:
2.9
通讯作者:
Liu, Ju
Liu, Ju
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Fuhong;Liu, Jing;Xiang, Hongjie;Sun, Zongguo;Li, Yan;Li, Xiao;Liu, Yanjun;Liu, Ju

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血脑屏障(BBB)损伤参与脓毒症相关脑病的发病机制。在这项研究中,我们使用青蒿素衍生物双氢青蒿素(DHA)治疗盲肠结扎穿孔(CLP)诱导的小鼠脓毒症模型和肿瘤坏死因子α(TNF-α)刺激的人脑微血管内皮细胞(hCMEC)/D3细胞系。我们发现,DHA降低BBB通透性,增加紧密连接蛋白闭合蛋白(OCLN)在CLP模型中的表达。在hCMEC/D3细胞中,DHA降低了TNF-α诱导的高通透性,并增加了OCLN的表达。DHA还抑制CLP小鼠模型和TNF-α刺激的hCMEC/D3细胞中的SNAI 1表达。这些数据表明,DHA通过刺激OCLN的表达,通过下调SNAI 1转录因子的表达,在脓毒症期间保护血脑屏障通透性。
Blood–brain barrier (BBB) injury is involved in the pathogenesis of sepsis‐associated encephalopathy. In this study, we used dihydroartemisinin (DHA), a derivative of artemisinin, to treat a cecal ligation and puncture (CLP)‐induced mouse sepsis model and a tumour necrosis factor α (TNF‐α)‐stimulated human cerebral microvessel endothelial cells (hCMEC)/D3 cell line. We found that DHA decreased BBB permeability and increased the expression of the tight junction protein occludin (OCLN) in the CLP model. In hCMEC/D3 cells, DHA decreased TNF‐α‐induced hyperpermeability and increased the expression of OCLN. DHA also repressed SNAI1 expression in the CLP mouse model and in TNF‐α‐stimulated hCMEC/D3 cells. These data suggest that DHA protects BBB permeability during sepsis by stimulating the expression of OCLN, by downregulating the expression of the SNAI1 transcription factor.
DOI: 10.1111/j.1530-0277.2011.01510.x
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