Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets
Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets
复制标题
DOI：
10.1038/pr.2017.104
复制
发表时间：
2017-07-01
影响因子：
3.6
通讯作者：
Martinez-Orgado, Jose
中科院分区：
文献类型：
--
作者：
Arruza, Luis;Ruth Pazos, Maria;Martinez-Orgado, Jose
背景：脑缺氧缺血（HI）损伤诱导新生猪远端炎性肺损伤。方法：新生仔猪在HI脑损伤后（颈动脉血流阻断和FiO 2 0.10持续30 min）静脉注射载体、CBD或CBD+ WAY 100635（5-HT 1A受体拮抗剂）。监测肺总顺应性（TLC）、氧合指数（01）和血管外肺含水量（EVLW）6 h。在脑和肺组织中评估组织学损伤、白细胞介素（IL）-1 β浓度和氧化应激。结果：CBD可预防HI对TLC和01的毒性作用，减轻肺组织学损伤，调节炎症反应（减少白细胞浸润和IL-1浓度），降低BALF和EVLW中的蛋白含量。这些作用与CBD诱导的脑内抗炎变化有关。HI不增加肺中的氧化应激。在肺，WAY 100635钝化CBD的有益效果，对组织学损伤，IL-1浓度，和EVLW.CONCLUSIONS：CBD减少脑HI诱导的远端肺损伤，5-HT 1A受体参与这些影响。CBD对肺部的影响是由于对大脑的抗炎作用还是由于对肺部的直接影响仍有待阐明。
BACKGROUND: Brain hypoxic ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.METHODS: Newborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO(2) 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (01), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1 beta concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).RESULTS: CBD prevented HI-induced deleterious effects on TLC and 01 and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.CONCLUSIONS: CBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.