Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy
Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy
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DOI：
10.1007/s12640-020-00293-y
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发表时间：
2020-10-06
影响因子：
3.7
通讯作者：
Petronilho, Fabricia
中科院分区：
文献类型：
--
作者：
Bonfante, Sandra;Joaquim, Larissa;Petronilho, Fabricia
脓毒症相关脑病是脓毒症的严重后果，由宿主对感染因子的反应触发，可导致脑损伤和认知障碍。脓毒症后免疫系统和脑之间的双向交流中存在多种机制，如神经炎症、氧化应激和线粒体功能障碍。斯钙素-1（STC-1）是一种内源性神经保护蛋白，通过诱导线粒体中的解偶联蛋白（UCPs）而起到抗炎和抑制超氧化物生成的作用。在这里，我们证明了STC-1在体外炎症反应中的保护作用，在LPS刺激的活化小胶质细胞中，以及在盲肠结扎穿孔（CLP）脓毒症动物模型大鼠海马中的神经炎症，氧化应激和线粒体功能，以及对长期记忆的影响。重组人STC-1（rhSTC 1）抑制LPS刺激的小胶质细胞中促炎细胞因子的产生，而不改变UCP-2的表达。此外，小脑延髓池注射rhSTC 1可减轻脓毒症后24 h海马急性炎症反应和氧化应激，并可增加线粒体呼吸链复合体I和II活性及肌酸激酶活性。rhSTC 1可有效预防CLP后的长期认知功能障碍。总之，rhSTC 1通过抑制小胶质细胞中的炎症反应并保护大鼠免受脓毒症相关脑病的影响而赋予显著的神经保护作用。
Sepsis-associated encephalopathy is a serious consequence of sepsis, triggered by the host response against an infectious agent, that can lead to brain damage and cognitive impairment. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after sepsis as neuroinflammation, oxidative stress, and mitochondrial dysfunction. Stanniocalcin-1 (STC-1), an endogen neuroprotective protein, acts as an anti-inflammatory and suppresses superoxide generation through induction of uncoupling proteins (UCPs) in the mitochondria. Here, we demonstrated a protective role of STC-1 on inflammatory responses in vitro, in activated microglia stimulated with LPS, and on neuroinflammation, oxidative stress, and mitochondrial function in the hippocampus of rats subjected to an animal model of sepsis by cecal ligation and puncture (CLP), as well the consequences on long-term memory. Recombinant human STC-1 (rhSTC1) suppressed the pro-inflammatory cytokine production in LPS-stimulated microglia without changing the UCP-2 expression. Besides, rhSTC1 injected into the cisterna magna decreased acute hippocampal inflammation and oxidative stress and increased the activity of complex I and II activity of mitochondrial respiratory chain and creatine kinase at 24 h after sepsis. rhSTC1 was effective in preventing long-term cognitive impairment after CLP. In conclusion, rhSTC1 confers significant neuroprotection by inhibiting the inflammatory response in microglia and protecting against sepsis-associated encephalopathy in rats.