七氟醚镇静通过稳定蛛网膜下腔出血模型中黏着连接蛋白β连环蛋白来减轻早期脑水肿形成：一项随机动物研究。
Sevoflurane sedation attenuates early cerebral oedema formation through stabilisation of the adherens junction protein beta catenin in a model of subarachnoid haemorrhage: A randomised animal study.
机构信息
From the Institute of Physiology and Zurich Centre for Integrative Human Physiology, University of Zurich (BBS, TR, BRZ, MS), Institute of Anaesthesiology, University Hospital Zurich, Zurich, Switzerland (BBS, TR, MS), Department of Anesthesiology, University of Illinois at Chicago, Chicago, USA (BBS) and Neurosurgical Intensive Care Unit, University Hospital Zurich, Zurich, Switzerland (CM, EK).
出版信息
Eur J Anaesthesiol. 2020 May;37(5):402-412. doi: 10.1097/EJA.0000000000001161.
BACKGROUND
Severe neurological impairment is a problem after subarachnoid haemorrhage (SAH). Although volatile anaesthetics, such as sevoflurane, have demonstrated protective properties in many organs, their use in cerebral injury is controversial. Cerebral vasodilation may lead to increased intracranial pressure (ICP), but at the same time volatile anaesthetics are known to stabilise the SAH-injured endothelial barrier.
OBJECTIVE
To test the effect of sevoflurane on ICP and blood-brain barrier function.
DESIGN
Randomised study.
PARTICIPANTS
One hundred male Wistar rats included, 96 analysed.
INTERVENTIONS
SAH was induced by the endoluminal filament method under ketamine/xylazine anaesthesia. Fifteen minutes after sham surgery or induction of SAH, adult male Wistar rats were randomised to 4 h sedation with either propofol or sevoflurane.
MAIN OUTCOME MEASURES
Mean arterial pressure (MAP), ICP, extravasation of water (small), Evan's blue (intermediate) and IgG (large molecule) were measured. Zonula occludens-1 (ZO-1) and beta-catenin (β-catenin), as important representatives of tight and adherens junction proteins, were determined by western blot.
RESULTS
Propofol and sevoflurane sedation did not affect MAP or ICP in SAH animals. Extravasation of small molecules was higher in SAH-propofol compared with SAH-sevoflurane animals (79.1 ± 0.9 vs. 78.0 ± 0.7%, P = 0.04). For intermediate and large molecules, no difference was detected (P = 0.6 and P = 0.2). Both membrane and cytosolic fractions of ZO-1 as well as membrane β-catenin remained unaffected by the injury and type of sedation. Decreased cytosolic fraction of β-catenin in propofol-SAH animals (59 ± 15%) was found to reach values of sham animals (100%) in the presence of sevoflurane in SAH animals (89 ± 21%; P = 0.04).
CONCLUSION
This experiment demonstrates that low-dose short-term sevoflurane sedation after SAH in vivo did not affect ICP and MAP and at the same time may attenuate early brain oedema formation, potentially by preserving adherens junctions.
TRIAL REGISTRATION
No 115/2014 Veterinäramt Zürich.
背景
蛛网膜下腔出血（SAH）后会出现严重的神经功能障碍。尽管挥发性麻醉剂，如七氟醚，在许多器官中显示出保护作用，但它们在脑损伤中的应用仍存在争议。脑血管扩张可能导致颅内压（ICP）升高，但同时挥发性麻醉剂已知可以稳定 SAH 损伤的内皮屏障。
目的
测试七氟醚对 ICP 和血脑屏障功能的影响。
设计
随机研究。
参与者
纳入 100 只雄性 Wistar 大鼠，96 只进行了分析。
干预措施
在氯胺酮/甲苯噻嗪麻醉下通过腔内纤维方法诱导 SAH。假手术或诱导 SAH 后 15 分钟，成年雄性 Wistar 大鼠随机接受 4 小时镇静，分别使用异丙酚或七氟醚。
主要观察指标
平均动脉压（MAP）、ICP、水外渗（小）、Evan's 蓝（中）和 IgG（大）。通过 Western blot 测定紧密连接和黏附连接蛋白的重要代表闭合蛋白-1（ZO-1）和β-连环蛋白（β-catenin）。
结果
异丙酚和七氟醚镇静对 SAH 动物的 MAP 或 ICP 没有影响。SAH-异丙酚组的小分子外渗高于 SAH-七氟醚组（79.1±0.9%比 78.0±0.7%，P=0.04）。对于中间和大分子，未检测到差异（P=0.6 和 P=0.2）。ZO-1 的膜和胞质部分以及膜 β-catenin 均不受损伤和镇静类型的影响。异丙酚-SAH 动物中β-catenin 的胞质部分减少（59±15%），在存在七氟醚的情况下，SAH 动物中的值达到 sham 动物的水平（100%，89±21%；P=0.04）。
结论
本实验表明，SAH 后体内低剂量短期七氟醚镇静不会影响 ICP 和 MAP，同时可能通过维持黏附连接来减轻早期脑水肿形成。
试验注册
苏黎世兽医局 No 115/2014。
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