Gut：肠道屏障受损是功能性消化不良的病生理机制

　　功能性消化不良（FD）是一种极其常见的功能性胃肠道疾病，我们对其病生理知之甚少。研究者推测肠道屏障功能损害通过诱导轻度炎症而参与了该疾病的起病和维持。因此，来自比利时的一项研究评价了FD患者的十二指肠黏膜完整性和轻度炎症。该研究结果对FD患者胃肠道不存在结构改变的经典认识提出了挑战。研究者认为肠道屏障功能受损是FD的一种病生理机制。因此恢复肠屏障完整性可能是FD患者治疗的一项可能靶标。该文2013年3月8日在线发表在《消化道》（GUT）杂志上。

　　研究者从满足罗马III标准的15名FD患者及15名年龄与性别匹配的健康对照中取得了十二指肠活检标本。在尤斯小室中测定了跨上皮电阻抗（TEER）及细胞旁通透性。实时定量PCR、western杂交和/或免疫荧光方法评价了细胞间黏附蛋白的表达。免疫组化方法评价了肥大细胞、嗜酸性粒细胞和上皮内淋巴细胞的数目。

　　结果与健康对照相比，FD患者TEER较低，细胞旁通透性增加，提示黏膜完整性受损。另外发现了紧密连接、黏着连接及桥粒水平异常表达的细胞间粘附蛋白。此外，黏膜内浸润增加的肥大细胞和嗜酸性粒细胞证实患者具有轻度炎症的特点。我们发现几种细胞间黏附蛋白的表达水平、通透性增加的程度与轻度炎症的程度之间具有显著相关性。

与消化不良相关的拓展阅读：

• 中国儿童功能性消化不良诊断和治疗共识

Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia

Objective 

Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD.

Design 

Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry.

Results 

Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found.

Conclusions 

These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.