Li Yan, Li Yan-Rong, Jin Yuan, Li Meng-Ying, Zhang Qian, Cao Jing, Li Fei, Zhang Hua, Chen Jing, Li Yun-Qing
Department of Anatomy, Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Department of Geriatrics, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China; Department of Human Anatomy, Basic Medical College, Zunyi Medical University, Zunyi 563006, China.
Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
J Chem Neuroanat. 2023 Mar;128:102235. doi: 10.1016/j.jchemneu.2023.102235. Epub 2023 Jan 18.
The enteric nervous system (ENS) is one of the important systems that regulate gastrointestinal function. The ENS is made up of enteric glial cells (EGCs) and neurons. For a long time, it was believed that the function of EGCs was only to give structural support to neurons. However, recent evidence indicates EGCs are involved in most gut functions, including the development and plasticity of the ENS, epithelial barrier, and motility. However, it remains unclear whether EGCs have the potential to modify colonic motility following irritable bowel syndrome (IBS) with predominant diarrhea (IBS-D). This study aimed to investigate changes in EGCs during IBS-D and assessed the effects of manipulating EGCs. An IBS-D rat model was constructed using acetic acid and restraint stress, and DL-fluorocitric acid (FC), an inhibitor of EGCs, was administered. The changes in EGCs and colonic motility were studied by employing techniques comprising morphological, molecular biological and functional experiments. The results showed significant activation of EGCs in the myenteric plexus (MP) of the IBS-D-induced rat colon with accelerated colonic motility. FC significantly reduced the activation of EGCs and colonic motility caused by acetic acid and restraint stress. Hypercontraction of the colon caused by IBS-D may be associated with activation of EGCs in the MP of the colon and this was prevented by FC. Therefore, regulating colon hypercontraction through interference with the activation of EGCs has significant prospects for clinical application to alleviate diarrhea in patients with IBS-D.
肠神经系统（ENS）是调节胃肠功能的重要系统之一。肠神经系统由肠胶质细胞（EGCs）和神经元组成。长期以来，人们认为肠胶质细胞的功能仅仅是为神经元提供结构支持。然而，最近的证据表明，肠胶质细胞参与了大多数肠道功能，包括肠神经系统的发育和可塑性、上皮屏障以及蠕动。然而，肠易激综合征腹泻型（IBS-D）后肠胶质细胞是否具有改变结肠蠕动的潜力仍不清楚。本研究旨在调查腹泻型肠易激综合征期间肠胶质细胞的变化，并评估操纵肠胶质细胞的效果。使用醋酸和束缚应激构建腹泻型肠易激综合征大鼠模型，并给予肠胶质细胞抑制剂DL-氟柠檬酸（FC）。采用形态学、分子生物学和功能实验等技术研究肠胶质细胞和结肠蠕动的变化。结果显示，腹泻型肠易激综合征诱导的大鼠结肠肌间神经丛（MP）中肠胶质细胞显著激活，结肠蠕动加速。FC显著降低了由醋酸和束缚应激引起的肠胶质细胞激活和结肠蠕动。腹泻型肠易激综合征引起的结肠过度收缩可能与结肠肌间神经丛中肠胶质细胞的激活有关，而FC可预防这种情况。因此，通过干扰肠胶质细胞的激活来调节结肠过度收缩在临床上缓解腹泻型肠易激综合征患者的腹泻方面具有重要的应用前景。
