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顽固性呕吐患者慢性胃电刺激期间的胃肠肽

Gastrointestinal Peptides During Chronic Gastric Electrical Stimulation in Patients With Intractable Vomiting.

作者信息

Meleine Mathieu, Melchior Chloé, Prinz Philip, Penfornis Alfred, Coffin Benoît, Stengel Andreas, Ducrotté Philippe, Gourcerol Guillaume

机构信息

Inserm UMR 1073, Institute for Innovation and Biomedical Research, Rouen University, Rouen, France.

Physiology Department, Rouen University Hospital, Rouen, France.

出版信息

Neuromodulation. 2017 Dec;20(8):774-782. doi: 10.1111/ner.12645. Epub 2017 Aug 10.

DOI:10.1111/ner.12645
PMID:28795473
Abstract

OBJECTIVES

Gastric electrical stimulation (GES) is an alternative therapy to treat patients with intractable vomiting. A preclinical study has demonstrated the modulation of the gastrointestinal (GI) peptide ghrelin by GES but such mechanism has never been investigated in patients. The aim of this work was to assess the effect of GES on GI peptide levels in patients with intractable vomiting.

MATERIALS AND METHODS

Twenty-one patients were randomized to receive either ON or OFF GES, 14 completed the study (10 ON, 4 OFF stimulation). Vomiting episodes, gastric emptying, and gastrointestinal quality of life index (GIQLI) were assessed. Gastric and blood samples were collected before and four months after the ON period of gastric stimulation. mRNA and/or peptide levels were assessed in gastric biopsies for ghrelin, leptin, and NUCB2/nesfatin-1 and in duodenal biopsies for glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) using RT-qPCR and multiplex technology. Ghrelin, leptin, GLP-1, PYY, gastric inhibitory peptide (GIP), and NUCB2/nesfatin-1 levels also were quantified in blood samples.

RESULTS

Among clinical parameters, vomiting episodes were slightly reduced by GES (p = 0.09). In tissue, mRNA or protein levels were not modified following chronic GES. In blood, a significant reduction of postprandial PYY levels (p < 0.05) was observed at M4 and a reduction of NUCB2/nesfatin-1 levels in fasted patients (p < 0.05). Increased plasma leptin levels after GES were correlated with reduction of vomiting and improvement of GIQLI.

CONCLUSIONS

GES reduces NUCB2/nesfatin-1 levels under fasting conditions and postprandial PYY levels in patients suffering from nausea and/or vomiting refractory to pharmacological therapies.

摘要

目的

胃电刺激(GES)是治疗顽固性呕吐患者的一种替代疗法。一项临床前研究已证明GES对胃肠(GI)肽胃饥饿素的调节作用,但这种机制从未在患者中进行过研究。这项工作的目的是评估GES对顽固性呕吐患者胃肠肽水平的影响。

材料和方法

21例患者被随机分为接受开启或关闭GES治疗,14例完成了研究(10例开启刺激,4例关闭刺激)。评估呕吐发作次数、胃排空及胃肠道生活质量指数(GIQLI)。在胃刺激开启期之前和四个月后采集胃和血液样本。使用逆转录定量聚合酶链反应(RT-qPCR)和多重技术评估胃活检组织中胃饥饿素、瘦素和核仁素2/nesfatin-1的mRNA和/或肽水平,以及十二指肠活检组织中胰高血糖素样肽1(GLP-1)和肽YY(PYY)的水平。还对血液样本中的胃饥饿素、瘦素、GLP-1、PYY、胃抑制肽(GIP)和核仁素2/nesfatin-1水平进行了定量。

结果

在临床参数中,GES使呕吐发作次数略有减少(p = 0.09)。在组织中,慢性GES后mRNA或蛋白质水平未发生改变。在血液中,在M4时观察到餐后PYY水平显著降低(p < 0.05),空腹患者的核仁素2/nesfatin-1水平降低(p < 0.05)。GES后血浆瘦素水平升高与呕吐次数减少和GIQLI改善相关。

结论

对于药物治疗无效的恶心和/或呕吐患者,GES可降低空腹条件下的核仁素2/nesfatin-1水平以及餐后PYY水平。

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