He Xiaogang, Cai Qiufang, Li Jianxiang, Guo Weifeng
Department of Neurology, Kunshan Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Kunshan, 215300, PR China.
Department of Neurology, Kunshan Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Kunshan, 215300, PR China.
Neurosci Lett. 2018 Feb 14;666:78-84. doi: 10.1016/j.neulet.2017.12.036. Epub 2017 Dec 16.
Cerebral infarction (CI) causes severe brain damage with high incidence. This study aimed to investigate the involvement of brain-gut axis in the treatment of CI by combined administration of β-asaron and paeonol. Rat middle cerebral artery occlusion (MCAO) model was established, the interleukin-1beta (IL-1β) and tumor necrosis factor α (TNF-α) in the rat peripheral blood were determined by ELISA assay, and brain tissue damage was evaluated by TUNNEL assay. The correlation of cholecystokinin (CCK) and nuclear factor-kappaB (NF-κB) signaling components between intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol were analyzed by quantitative RT-PCR and western blotting. In vitro transwell co-culture was performed to confirm the correlated expression. The expression of CCK and NF-κB signaling components were closely correlated between the intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol. The combined administration also regulates the IL-1β and TNF-α in the MCAO rat peripheral blood and ameliorate the brain damage in MCAO rats. Elevated expression of related genes was observed in the cortical neurons co-cultured with intestinal mucosal epithelial cells treated by β-asaron and paeonol. The brain-gut axis mediates the therapeutic effect of β-asaron and paeonol for cerebral infarction through CCK and NF-κB signaling.
脑梗死（CI）发病率高，会导致严重的脑损伤。本研究旨在探讨脑-肠轴在联合应用β-细辛醚和丹皮酚治疗CI中的作用。建立大鼠大脑中动脉闭塞（MCAO）模型，采用酶联免疫吸附测定（ELISA）法测定大鼠外周血白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNF-α），采用隧道试验（TUNNEL）评估脑组织损伤。通过定量逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法分析β-细辛醚和丹皮酚治疗的MCAO大鼠肠黏膜与前额叶皮质之间胆囊收缩素（CCK）和核因子κB（NF-κB）信号成分的相关性。进行体外Transwell共培养以确认相关表达。β-细辛醚和丹皮酚治疗的MCAO大鼠肠黏膜与前额叶皮质之间CCK和NF-κB信号成分的表达密切相关。联合给药还可调节MCAO大鼠外周血中的IL-1β和TNF-α，并改善MCAO大鼠的脑损伤。在用β-细辛醚和丹皮酚处理的肠黏膜上皮细胞共培养的皮质神经元中观察到相关基因的表达升高。脑-肠轴通过CCK和NF-κB信号介导β-细辛醚和丹皮酚对脑梗死的治疗作用。
