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功能性消化不良(FD)患者中瞬时受体电位香草酸(TRPV)表达上调和脑源性神经营养因子(BDNF)表达下调。

Up-regulation of transient receptor potential vanilloid (TRPV) and down-regulation of brain-derived neurotrophic factor (BDNF) expression in patients with functional dyspepsia (FD).

机构信息

Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.

Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Neurogastroenterol Motil. 2018 Feb;30(2). doi: 10.1111/nmo.13176. Epub 2017 Aug 7.

DOI:10.1111/nmo.13176
PMID:28782273
Abstract

BACKGROUND

The role of immune activation in Functional Dyspepsia (FD) patients without previous infection is unclear. We compare the gastric and circulating brain-derived neurotropic factor (BDNF), receptor potential vanilloid type (TRPV) families and various cytokines in FD patients.

METHODS

Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Helicobacter pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Corpus biopsies and serum samples were collected.

KEY RESULTS

Forty three [M:F=8:35, mean age: 35.0 (9.3)] FD patients were compared with 23 healthy controls [M:F=8:15, mean age: 36.6 (10.2)]. FD patients had postprandial distress syndrome (PDS) as predominant sub-type (PDS: 36, EPS: 2). There was no significant difference in the median inflammation score (FD:0 (0-1) vs Control:0 (0-1), P=.79). However, FD patients had significantly higher mRNA expression of TRPV1 (FD:0.014±0.007, Control:0.003±0.001, 4.6 fold, P=.02) and TRPV2 (FD:0.012±0.006, Control:0.003±0.001, 4 fold, P=.02) compared to controls. The serum (FD:258.0±12.3 ng ml , Control:319.7±18.1 ng ml , P<.01) and gastric BDNF mRNA (FD:0.06±0.008, Control:0.092±0.01, 0.65 fold, P=.02)levels significantly lower in FD patients. Secretion of cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, G-CSF, TGF-β2, MCP-1)was also highly correlated with dyspeptic symptoms in patients with FD.

CONCLUSIONS & INFERENCES: Despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in FD patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection.

摘要

背景

免疫激活在既往无感染的功能性消化不良(FD)患者中的作用尚不清楚。我们比较了 FD 患者的胃和循环中的脑源性神经营养因子(BDNF)、香草素受体家族(TRPV)和各种细胞因子。

方法

连续招募了无近期肠胃炎史且无症状的成年 FD 患者(罗马 III 标准)和健康对照者进行上消化道内镜检查。排除 GERD 和 IBS 为主诉、糖尿病、目前或既往幽门螺杆菌感染、精神疾病以及近期使用 NSAID 或 PPI 的患者。采集胃体活检组织和血清样本。

主要结果

43 例 FD 患者(8 例男性,35 例女性,平均年龄 35.0(9.3)岁)与 23 例健康对照者(8 例男性,15 例女性,平均年龄 36.6(10.2)岁)进行了比较。FD 患者以餐后不适综合征(PDS)为主(PDS:36 例,EPS:2 例)。FD 患者的炎症评分中位数无显著差异(FD:0(0-1)vs 对照组:0(0-1),P=0.79)。然而,FD 患者的 TRPV1(FD:0.014±0.007,对照组:0.003±0.001,4.6 倍,P=0.02)和 TRPV2(FD:0.012±0.006,对照组:0.003±0.001,4 倍,P=0.02)mRNA 表达明显高于对照组。FD 患者的血清(FD:258.0±12.3ng/ml,对照组:319.7±18.1ng/ml,P<0.01)和胃 BDNF mRNA(FD:0.06±0.008,对照组:0.092±0.01,0.65 倍,P=0.02)水平显著低于 FD 患者。FD 患者的细胞因子(IL-4、IL-5、IL-6、IL-8、IL-10、G-CSF、TGF-β2、MCP-1)分泌也与消化不良症状高度相关。

结论

尽管 FD 患者无胃黏膜炎症,但我们观察到 TRPV1 和 TRPV2 的上调以及 BDNF 的下调。这些提示免疫改变可能与既往无感染的 FD 的发病机制有关。

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