Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis

Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis
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早期口服营养通过 TRPA1/CCK1-R 介导的肥大细胞神经轴改善术后肠梗阻

DOI:
10.21037/atm.2020.01.95
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发表时间:
2020-02
影响因子:
--
通讯作者:
Xu Peng-Yuan
Xu Peng-Yuan
中科院分区:
医学4区
文献类型:
--
作者:
Sun Da-Li;Qi Yu-Xing;Yang Ting;Lin Yue-Ying;Li Shu-Min;Li Yi-Jun;Xu Qing-Wen;Sun Yan-Bo;Li Wei-Ming;Chen Xiong-Zhi;Xu Peng-Yuan

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背景早期口服营养通过调节肥大细胞-神经轴改善术后肠梗阻(POI)的机制尚不清楚。本研究旨在探讨早期口服营养是否通过调节肥大细胞-神经轴上的瞬时受体电位锚蛋白1(TRPA 1)/胆囊收缩素1受体(CCK 1-R)来改善POI。方法实验1:雄性SD大鼠随机分为TRPA 1抑制剂+口服营养组(TI + ON + POI)、口服营养组(ON + POI)、POI组(POI)和假手术组(Sham)。每组9只大鼠接受治疗。实验二:建立肥大细胞和背根神经节细胞的原代培养体系,建立非接触共培养体系。将细胞分为背根神经节(DRG)组、肥大细胞组、DRG +肥大细胞组、TRPA 1抑制剂或增强剂组、肥大细胞稳定剂或增强剂组、CCK 1-R抑制剂或增强剂组。分析结肠组织、门静脉血、培养上清或背根神经节中TRPA 1、CCK 1-R和组胺的表达、肠转运试验和肥大细胞形态学的结果。结果实验1早期口服营养可减轻肥大细胞的脱颗粒和活化,减轻肠壁肌肉的炎症反应(P<0.05)。早期口服营养通过用TRPA 1稳定肥大细胞来改善POI。TRPA 1抑制剂降低门静脉血CCK 1-R浓度和结肠平滑肌CCK 1-R表达(P<0.05)。实验2中,肥大细胞功能的改变调节神经元CCK 1-R的分泌,CCK 1-R负性调节肥大细胞的脱颗粒和活化(P<0.05),肥大细胞正性调节DRG中TRPA 1蛋白的表达(P<0.05)。结论早期肠内营养可通过TRPA 1/CCK 1-R介导的肥大细胞-神经轴改善POI。TRPA 1正调控CCK 1-R以稳定肥大细胞,但TRPA 1不是下游CCK 1-R通路的靶点。
Background The mechanism of early oral nutrition that regulates the mast cell-nerve axis to improve postoperative ileus (POI) remains unclear. This study aims to investigate whether early oral nutrition can improve POI through Transient receptor potential ankyrin-1 (TRPA1)/cholecystokinin 1 receptor (CCK1-R) in the mast cell-nerve axis. Methods Experiment 1: Male Sprague-Dawley (SD) rats were randomly divided into the TRPA1 inhibitor + oral nutrition group (TI + ON + POI), oral nutrition group (ON + POI), POI group (POI) and sham surgery group (Sham). Nine rats in each group were treated. Experiment 2: Primary cultures of mast cells and dorsal root ganglion cells were created, and a non-contact co-culture system was established. The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. The results of expression of TRPA1, CCK1-R and histamine in colon tissue, portal vein blood, supernatant or dorsal root ganglia, intestinal transport test and mast cell morphology were analysed. Results In experiment 1, Early oral nutrition could alleviate the degranulation and activation of mast cells and alleviate the inflammatory reaction of intestinal wall muscles (P<0.05). Early oral nutrition improved POI by stabilizing mast cells with TRPA1. TRPA1 inhibitor decreased CCK1-R concentrations in portal vein blood and CCK1-R expression in colonic smooth muscle (P<0.05). In experiment 2, the change in mast cell function regulated the secretion of CCK1-R by neurons, CCK1-R negatively regulated the degranulation and activation of mast cells (P<0.05), and mast cells positively regulated the expression of TRPA1 protein in DRG (P<0.05). Conclusions Early enteral nutrition can improve POI through the TRPA1/CCK1-R-mediated mast cell-nerve axis. TRPA1 positively regulates CCK1-R to stabilize mast cells, but TRPA1 is not the target of the downstream CCK1-R pathway.
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Ceccarelli S;Panera N;Mina M;Gnani D;De Stefanis C;Crudele A;Rychlicki C;Petrini S;Bruscalupi G;Agostinelli L;Stronati L;Cucchiara S;Musso G;Furlanello C;Svegliati-Baroni G;Nobili V;Alisi A
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