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
Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
Yunnan Research Center for Surgical Clinical Nutrition, Kunming 650101, China.
Ann Transl Med. 2020 Mar;8(5):179. doi: 10.21037/atm.2020.01.95.
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.
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.
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).
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.
早期口服营养调节肥大细胞 - 神经轴以改善术后肠梗阻（POI）的机制尚不清楚。本研究旨在探讨早期口服营养是否能通过肥大细胞 - 神经轴中的瞬时受体电位锚蛋白1（TRPA1）/胆囊收缩素1受体（CCK1 - R）改善POI。
实验1：雄性Sprague - Dawley（SD）大鼠随机分为TRPA1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2：建立肥大细胞和背根神经节细胞的原代培养，并建立非接触共培养系统。细胞分为背根神经节（DRG）组、肥大细胞组、DRG + 肥大细胞组、TRPA1抑制剂或增强剂组、肥大细胞稳定剂或增强剂组、CCK1 - R抑制剂或增强剂组。分析结肠组织、门静脉血、上清液或背根神经节中TRPA1、CCK1 - R和组胺的表达结果、肠道运输试验和肥大细胞形态。
在实验1中，早期口服营养可减轻肥大细胞的脱颗粒和活化，并减轻肠壁肌肉的炎症反应（P<0.05）。早期口服营养通过用TRPA1稳定肥大细胞来改善POI。TRPA1抑制剂降低门静脉血中CCK1 - R浓度和结肠平滑肌中CCK1 - R表达（P<0.05）。在实验2中，肥大细胞功能的变化调节神经元分泌CCK1 - R，CCK1 - R负向调节肥大细胞的脱颗粒和活化（P<0.05），肥大细胞正向调节DRG中TRPA1蛋白的表达（P<0.05）。
早期肠内营养可通过TRPA1/CCK1 - R介导的肥大细胞 - 神经轴改善POI。TRPA1正向调节CCK1 - R以稳定肥大细胞，但TRPA1不是下游CCK1 - R途径的靶点。
