Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
Cannabis Cannabinoid Res. 2023 Jun;8(3):510-526. doi: 10.1089/can.2021.0085. Epub 2022 Apr 20.
Our laboratory investigates changes in the respiratory pattern during systemic inflammation in various rodent models. The endogenous cannabinoid system (ECS) regulates cytokine production and mitigates inflammation. Inflammation not only affects cannabinoid (CB) 1 and CB2 receptor gene expression ( and ), but also increases the predictability of the ventilatory pattern. Our primary objective was to track ventilatory pattern variability and transcription of and , and of , , and tumor necrosis factor-alpha ( mRNAs at multiple time points in central and peripheral tissues during systemic inflammation induced by peritonitis. In male Sprague Dawley rats (=24), we caused peritonitis by implanting a fibrin clot containing either 0 or 25×10 intraperitoneally. We recorded breathing with whole-animal plethysmography at baseline and 1 h before euthanasia. We euthanized the rats at 3, 6, or 12 h after inoculation and harvested the pons, medulla, lung, and heart for gene expression analysis. With peritonitis, more than was correlated to , , and mRNAs in medulla, pons, and lung and changed oppositely in the pons, medulla, and lung. These changes were associated with increased predictability of ventilatory pattern. Specifically, nonlinear complexity index correlated with increased mRNA in the pons and medulla, and coefficient of variation for cycle duration correlated with and mRNAs in the lung. The mRNAs for ECS receptors varied with time during the central and peripheral inflammatory response to peritonitis. These changes occurred in the brainstem, which contains the network that generates breathing pattern and thus, may participate in ventilatory pattern changes during systemic inflammation.
我们的实验室研究了在各种啮齿动物模型中全身炎症期间呼吸模式的变化。内源性大麻素系统（ECS）调节细胞因子的产生并减轻炎症。炎症不仅影响大麻素（CB）1 和 CB2 受体基因的表达（和），而且还增加了通气模式的可预测性。我们的主要目标是在腹膜炎引起的全身炎症期间，在中央和外周组织的多个时间点跟踪通气模式变异性和转录物和的转录，以及的、和肿瘤坏死因子-α（mRNA。在雄性 Sprague Dawley 大鼠（n=24）中，我们通过将含有 0 或 25×10 的纤维蛋白凝块腹膜内植入来引起腹膜炎。我们在基线和安乐死前 1 小时用全动物体积描记术记录呼吸。在接种后 3、6 或 12 小时处死大鼠，并收获脑桥、延髓、肺和心脏进行基因表达分析。在腹膜炎中，与 mRNA 的相关性超过 ，在延髓、脑桥和肺中与和 mRNA 相关，并且在脑桥、延髓和肺中变化相反。这些变化与通气模式可预测性的增加有关。具体来说，非线性复杂度指数与脑桥和延髓中增加的 mRNA 相关，而周期持续时间的变异系数与肺中的和 mRNA 相关。ECS 受体的 mRNA 在腹膜炎引起的中枢和外周炎症反应期间随时间变化。这些变化发生在脑干中，脑干包含产生呼吸模式的网络，因此可能参与全身炎症期间通气模式的变化。
