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慢性结肠炎引起的内脏疼痛与缓解期的焦虑增加有关。

Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase.

机构信息

Institut National de la Santé et de la Recherche Médicale Unit 1073 "Digestive Tract Environment and Nutrition," Normandie University, UNIROUEN, France.

Institute for Research and Innovation in Biomedicine, Normandie University, Union Nationale Inter-Universitaire Rouen , Rouen , France.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2019 Jun 1;316(6):G692-G700. doi: 10.1152/ajpgi.00248.2018. Epub 2019 Feb 8.

Abstract

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15-45 mg of TNBS) in 30 rats, whereas the control rats ( = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced ) a visceral hypersensitivity ( = 0.03), ) an increased colon weight-to-length ratio ( = 0.01), ) higher inflammatory and fibrosis scores ( = 0.0390 and = 0.0016, respectively), and ) a higher colonic IL-6 and IL-10 production ( = 0.008 and = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae. Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

摘要

炎症性肠病(IBD)的特征是反复发作和缓解期,导致慢性炎症后后遗症。在炎症后后遗症中,三分之一的 IBD 患者存在持续缓解期的功能性症状或心理合并症。我们研究的目的是评估慢性结肠炎在安静肠道炎症的大鼠中的功能性和行为后遗症。通过每周一次直肠内注射逐渐增加浓度的三硝基苯磺酸(TNBS),在 30 只大鼠中诱导慢性结肠炎 3 周(15-45mgTNBS),而对照组大鼠(=24)接受载体。在 TNBS 后 50 天,通过结肠扩张的内脏运动反应评估内脏敏感性,并在结肠和背根神经节中定量测定瞬时受体电位香草酸型 1(TRPV1)表达。通过研究肠道通透性、紧密连接蛋白、髓过氧化物酶活性、组织学评分和细胞因子产生(IL-6、IL-10 和 TNF-α)来评估屏障功能和炎症反应。从最后一次 TNBS 注射后 50 天到 64 天进行焦虑行为测试。慢性 TNBS 诱导)内脏高敏感(=0.03),)结肠重量-长度比增加(=0.01),)炎症和纤维化评分较高(=0.0390 和=0.0016,分别),)结肠 IL-6 和 IL-10 产生增加(=0.008 和=0.005,分别)与对照组大鼠相比。肠道通透性、结肠 TNF-α 产生、髓过氧化物酶活性和 TRPV1 表达在各组之间无差异。慢性 TNBS 在旷场试验和声学应激试验中增加了焦虑相关行为。总之,慢性结肠炎引起内脏高敏感和焦虑增加等功能性后遗症,伴有低度肠道炎症。开发代表性的动物模型将使我们能够确定治疗方法,以更好地管理 IBD 相关后遗症。患有炎症性肠病的患者生活质量受损。控制黏膜炎症的治疗进展为我们提供了一个机会,以开发新的方法来了解炎症后后遗症背后的机制。我们使用慢性结肠炎模型来研究对内脏疼痛、肠道屏障功能和心理影响的长期后遗症。慢性结肠炎在缓解期引起功能性症状和焦虑增加。它可能定义新的治疗方法,以更好地管理炎症性肠病相关后遗症。

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