炎症细胞因子参与二氢辣椒素（DHC）和区域冷却输注（RCI）诱导的缺血性大鼠神经保护作用。
Inflammatory cytokines are involved in dihydrocapsaicin (DHC) and regional cooling infusion (RCI)-induced neuroprotection in ischemic rat.
机构信息
China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, China; Center of Stroke, Beijing Institute for Brain Disorders, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
出版信息
Brain Res. 2019 May 1;1710:173-180. doi: 10.1016/j.brainres.2018.12.033. Epub 2018 Dec 22.
OBJECTIVE
The combination of pharmacological hypothermia - dihydrocapsaicin (DHC) and intra-arterial regional cooling infusions (RCI) was found to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection in acute ischemic stroke. The aim of this study was to explore whether the combination could induce a long-term neuroprotective effects, as well as the underlying mechanism.
METHODS
Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament. The ischemic rats were randomized to receive pharmacological hypothermia by intraperitoneal (i.p.) injection of DHC, physical hypothermia by RCI of 6 ml cold saline (4 °C), the combination, and no treatment. Over a 21-day period, brain damage was determined by infarct volume with MRI, and neurological deficit with grid-walking and beam balance tests. Blood brain barrier (BBB) was assessed by Evans-Blue (EB) contents. Inflammatory cytokines were determined in peri-infarct area by antibody array and ELISA.
RESULTS
The combination of DHC and RCI reduced (p < 0.05) infarct volume and neurologic deficit after stroke. BBB leakage and pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) were significantly decreased (p < 0.05) because of the combination, while protective cytokines (IL-4 and IL-10) were increased (p < 0.05) in the peri-infarct area.
CONCLUSIONS
The combination approach enhanced the efficacy of hypothermia-induced neuroprotection following ischemic stroke. Our findings provide a hint to translate the combination method from bench to bedside.
目的
研究发现，药理学低温-二氢辣椒素（DHC）与动脉内区域性冷却输注（RCI）联合使用可提高低温效率和低温诱导的缺血性脑卒中神经保护作用。本研究旨在探讨联合应用是否能诱导长期的神经保护作用及其潜在机制。
方法
采用腔内空心丝法对 Sprague-Dawley 大鼠进行大脑中动脉闭塞（MCAO）2 小时。将缺血性大鼠随机分为腹腔（i.p.）注射 DHC 进行药理学低温、4°C 冷生理盐水 RCI 进行物理低温、联合治疗和未治疗组。在 21 天的时间里，通过 MRI 确定脑损伤程度，通过网格行走和横梁平衡测试确定神经功能缺损程度。通过 Evans-Blue（EB）含量评估血脑屏障（BBB）。通过抗体阵列和 ELISA 测定梗塞周围区域的炎症细胞因子。
结果
DHC 和 RCI 的联合应用降低了（p<0.05）中风后梗死体积和神经功能缺损。由于联合应用，BBB 渗漏和促炎细胞因子（IFN-γ、IL-2 和 TNF-α）显著减少（p<0.05），而保护细胞因子（IL-4 和 IL-10）在梗塞周围区域增加（p<0.05）。
结论
联合应用方法增强了缺血性脑卒中后低温诱导神经保护的疗效。我们的发现为将联合方法从实验室转化到临床提供了线索。
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