Johnson John C, Geesala Ramasatyaveni, Zhang Ke, Lin You-Min, M'Koma Amosy E, Shi Xuan-Zheng
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States.
John Sealy School of Medicine Class of 2025, University of Texas Medical Branch, Galveston, TX, United States.
Front Physiol. 2023 Jul 14;14:1215900. doi: 10.3389/fphys.2023.1215900. eCollection 2023.
Gut smooth muscle dysfunctions contribute to symptoms such as abdominal cramping, diarrhea, and constipation in inflammatory bowel disease (IBD). The mechanisms for muscle dysfunctions are incompletely understood. We tested the hypothesis that mechanical stress plays a role in muscle dysfunction in a rat model of Crohn's-like colitis where inflammatory stenosis leads to mechanical distention in the pre-inflammation site. Crohn's-like colitis was induced by intracolonic instillation of TNBS (65 mg/kg) in Sprague-Dawley rats. Control rats were instilled with saline. The rats were fed with either regular solid food or exclusively liquid diet. Rats were euthanized by day 7. When rats were fed with solid food, TNBS treatment induced localized transmural inflammation with stenosis in the instillation site and marked distention with no inflammation in the pre-inflammation site of the colon. Smooth muscle contractility was suppressed, and expression of cyclo-oxygenase-2 (COX-2) and production of prostaglandin E (PGE) were increased not only in the inflammation site but also in the pre-inflammation site. Liquid diet treatment, mimicking exclusive enteral nutrition, completely released mechanical distention, eliminated COX-2 expression and PGE production, and improved smooth muscle contractility especially in the pre-inflammation site. When rats were administered with COX-2 inhibitor NS-398 (5 mg/kg, i. p. daily), smooth muscle contractility was restored in the pre-inflammation site and significantly improved in the inflammation site. Colonic smooth muscle contractility is significantly impaired in stenotic Crohn's-like colitis rats not only in the inflammation site, but in the distended pre-inflammation site. Mechanical stress-induced expression of COX-2 plays a critical role in smooth muscle dysfunction in the pre-inflammation site in Crohn's-like colitis rats.
肠道平滑肌功能障碍会导致炎症性肠病（IBD）出现腹部绞痛、腹泻和便秘等症状。肌肉功能障碍的机制尚未完全明确。我们在克罗恩病样结肠炎大鼠模型中测试了机械应力在肌肉功能障碍中起作用的假说，在该模型中，炎症性狭窄会导致炎症前部位出现机械性扩张。通过向Sprague-Dawley大鼠结肠内注入三硝基苯磺酸（TNBS，65mg/kg）诱导克罗恩病样结肠炎。对照大鼠注入生理盐水。给大鼠喂食常规固体食物或仅喂液体饮食。在第7天对大鼠实施安乐死。当给大鼠喂食固体食物时，TNBS处理会在注入部位诱发局限性透壁性炎症并伴有狭窄，在结肠炎症前部位则出现明显扩张但无炎症。平滑肌收缩性受到抑制，不仅在炎症部位，而且在炎症前部位，环氧化酶-2（COX-2）的表达和前列腺素E（PGE）的产生均增加。模拟全肠内营养的液体饮食处理完全解除了机械性扩张，消除了COX-2表达和PGE产生，并改善了平滑肌收缩性，尤其是在炎症前部位。当给大鼠腹腔注射COX-2抑制剂NS-398（5mg/kg，每日一次）时，炎症前部位的平滑肌收缩性得以恢复，炎症部位也显著改善。在狭窄的克罗恩病样结肠炎大鼠中，结肠平滑肌收缩性不仅在炎症部位，而且在扩张的炎症前部位均受到显著损害。机械应力诱导的COX-2表达在克罗恩病样结肠炎大鼠炎症前部位的平滑肌功能障碍中起关键作用。
