Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein-induced Inflammation through a Vagomimetic Action in Mice.
Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein-induced Inflammation through a Vagomimetic Action in Mice.
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DOI：
10.1097/aln.0000000000002038
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发表时间：
2018-05
期刊：
影响因子：
8.8
通讯作者：
Maze M
中科院分区：
文献类型：
--
作者：
Hu J;Vacas S;Feng X;Lutrin D;Uchida Y;Lai IK;Maze M
由损伤相关分子模式引发的炎症与手术创伤和严重疾病相关的认知能力下降有关。我们确定炎症的消退是否介导右美托咪定诱导的损伤相关分子模式诱导的认知衰退的减少。在接受神经（迷走神经）和体液炎症解决途径阻断剂的小鼠中，高分子组 Box 1 蛋白（一种与损伤相关的分子模式）诱导认知能力下降（通过微量恐惧条件评估）。通过促炎细胞因子评估全身和神经炎症。右美托咪定逆转了损伤相关的分子模式诱导的认知能力下降和炎症（平均值±标准差）（微量恐惧调节：58.77±8.69% vs 41.45±7.64%，p<0.0001；血浆IL-1β：7.0±2.2pg/ml vs 49.8±6.0pg/ml，p<0.0001； 血浆 IL-6：3.2 ± 1.6pg/ml vs 19.5 ± 1.7pg/ml，p<0.0001；海马 IL-1β：4.1 ± 3.0 pg/mg 对比 41.6 ± 8.0 pg/mg，p<0.0001；海马 IL-6：3.4 ± 1.3 pg/mg 对比 16.2 ± 2.7pg/mg，p < 0.0001）。右美托咪定的逆转可通过阻断拟迷走咪唑啉和α7烟碱乙酰胆碱受体来预防，但不能通过α2肾上腺素受体阻断来预防。 Netrin-1 是炎症消退的协调者，被右美托咪定上调（倍数变化）（肺：1.5 ± 0.1 vs 0.7 ± 0.1，p <0.0001；脾：1.5 ± 0.2 vs 0.6 ± 0.2，p <0.0001），导致促消退（lipoxin-A4：1.7 ± 0.2 与 0.9 ± 0.2，p<0.0001）和促炎体液介质（白三烯-B4：1.0±0.2 vs 3.0±0.3，p<0.0001）的下调，这是通过α7烟碱乙酰胆碱受体阻断来预防的。右美托咪定通过拟迷走神经（神经）和体液途径解决炎症，从而防止损伤相关的分子模式介导的认知能力下降。
Inflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern-induced cognitive decline. Cognitive decline (assessed by trace fear-conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by pro-inflammatory cytokines. Damage-associated molecular pattern-induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear-conditioning: 58.77 ± 8.69% vs 41.45 ± 7.64%, p<0.0001; plasma IL-1β: 7.0 ± 2.2 pg/ml vs 49.8 ± 6.0pg/ml, p < 0.0001; plasma IL-6: 3.2 ± 1.6pg/ml vs 19.5 ± 1.7pg/ml, p<0.0001; hippocampal IL-1β: 4.1 ± 3.0pg/mg vs 41.6 ± 8.0pg/mg, p<0.0001; hippocampal IL-6: 3.4 ± 1.3pg/mg vs 16.2 ± 2.7pg/mg, p < 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α7 nicotinic acetylcholine receptors but not by α2 adrenoceptor-blockade. Netrin-1, the orchestrator of inflammation-resolution, was upregulated (fold-change) by dexmedetomidine (Lung: 1.5 ± 0.1 vs 0.7 ± 0.1, p<0.0001; Spleen: 1.5 ± 0.2 vs 0.6 ± 0.2, p<0.0001) resulting in upregulation of pro-resolving (lipoxin-A4: 1.7 ± 0.2 vs 0.9 ± 0.2, p<0.0001) and down-regulation of pro-inflammatory (leukotriene-B4: 1.0 ± 0.2 vs 3.0 ± 0.3, p<0.0001) humoral mediators that was prevented by α7 nicotinic acetylcholine receptor-blockade. Dexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways thereby preventing damage-associated molecular pattern-mediated cognitive decline.
老年患者（HIPELD）研究的髋部骨折手术：一项随机多中心对照试验的方案，该试验评估了氙气对髋部骨折手术的老年患者的术后del妄的影响。
影响因子：
2.5
作者：
Coburn M;Sanders RD;Maze M;Rossaint R;HIPELD Investigators
通讯作者：
HIPELD Investigators