急性肠道感染后短暂的应激导致大鼠回肠中胆碱能和肽能神经递质的改变依赖于肥大细胞。

Alteration of cholinergic and peptidergic neurotransmitters in rat ileum induced by acute stress following transient intestinal infection is mast cell dependent.

机构信息

Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Chin Med J (Engl). 2010 Jan 20;123(2):227-33.

PMID:20137376

Abstract

BACKGROUND

Mast cells are implicated in the development of irritable bowel syndrome (IBS), which is associated with the activation of the "neural-immune" system. The aim of this study was to investigate the role of mast cells in the remodeling of cholinergic and peptidergic neurotransmitters induced by acute cold restriction stress (ACRS) post infection (PI) using mast cell deficient rats (Ws/Ws) and their wild-type controls (+/+).

METHODS

Transient intestinal infection was initiated by giving 1500 Trichinella spiralis (T.S.) larvae by gavage. ACRS was induced for 2 hours at day 100 PI. Samples of terminal ilea were prepared for H&E staining, mast cell counting and activation and assessment of IL-1beta and IL-10.

RESULTS

When infected, both strains of rats experienced an acute infectious stage followed by a recovery. Histological scores were significantly higher in infected rats compared with those of the non-infected controls at day 10 PI (10 day-PI vs. control: +/+: 2.75+/-0.17 vs. 0.42+/-0.09; Ws/Ws: 2.67+/-0.67 vs. 0.50+/-0.34; P<0.01). In +/+ rats, post-infection ACRS induced the formation of low-grade inflammation, represented by the imbalance of IL-1beta and IL-10 (IL-1beta: PI+ACRS vs. control: (1812.24+/-561.61) vs. (1275.97+/-410.21) pg/g, P<0.05; IL-10: PI+ACRS vs. control: (251.9+/-39.8) vs. (255.3+/-24.7) pg/g, P>0.05), accompanied by hyperplasia and activation of mast cells (PI+ACRS vs. control: 58.8+/-19.2 vs. 28.0+/-7.6; P<0.01). The balance between acetylcholine (ACh) and substance P (SP) was also disturbed (ACh: PI+ACRS vs. control: (743.94+/-238.72) vs. (1065.68+/-256.46) pg/g, P<0.05; SP: PI+ACRS vs. control: (892.60+/-231.12) vs. (696.61+/-148.61) pg/g, P<0.05). Nevertheless, similar changes of IL-1beta/IL-10 and ACh/SP were not detected in Ws/Ws rats.

CONCLUSION

The imbalance of ACh/SP, together with the activation of mucosal immunity induced by post-infection ACRS were lacking in mast cell deficient rats, which supports the premise that mast cells play an important role in cholinergic and peptidergic remodeling in the ileum of rats.

摘要

背景

肥大细胞参与肠易激综合征（IBS）的发展，其与“神经免疫”系统的激活有关。本研究旨在探讨肥大细胞在感染后急性冷限制应激（ACRS）诱导的胆碱能和肽能神经递质重构中的作用，使用肥大细胞缺陷大鼠（Ws/Ws）及其野生型对照（+/+）。

方法

通过灌胃给予 1500 条旋毛虫幼虫来引发短暂的肠道感染。在感染后第 100 天，进行 2 小时的 ACRS。制备末端回肠样本进行 H&E 染色、肥大细胞计数和激活，并评估 IL-1β和 IL-10。

结果

感染后，两种大鼠均经历了急性感染期，随后恢复。与非感染对照组相比，感染大鼠在感染后第 10 天（10 天-PI 与对照组相比：+/+：2.75+/-0.17 比 0.42+/-0.09；Ws/Ws：2.67+/-0.67 比 0.50+/-0.34；P<0.01）的组织学评分显著更高。在+/+大鼠中，感染后 ACRS 诱导形成低级别炎症，表现为 IL-1β和 IL-10 的失衡（IL-1β：PI+ACRS 与对照组相比：（1812.24+/-561.61）比（1275.97+/-410.21）pg/g，P<0.05；IL-10：PI+ACRS 与对照组相比：（251.9+/-39.8）比（255.3+/-24.7）pg/g，P>0.05），同时伴有肥大细胞的增生和激活（PI+ACRS 与对照组相比：58.8+/-19.2 比 28.0+/-7.6；P<0.01）。乙酰胆碱（ACh）和 P 物质（SP）之间的平衡也受到干扰（ACh：PI+ACRS 与对照组相比：（743.94+/-238.72）比（1065.68+/-256.46）pg/g，P<0.05；SP：PI+ACRS 与对照组相比：（892.60+/-231.12）比（696.61+/-148.61）pg/g，P<0.05）。然而，在 Ws/Ws 大鼠中未检测到类似的 IL-1β/IL-10 和 ACh/SP 变化。