aDepartment of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht bDepartment of Gastroenterology, Saint Antonius Hospital, Nieuwegein, The Netherlands cMedical Department IV, Campus Innenstadt, LMU University Clinic Munich, Munich, Germany dDiscipline of Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.
Eur J Gastroenterol Hepatol. 2014 Feb;26(2):205-12. doi: 10.1097/MEG.0000000000000001.
Dyspeptic symptoms are frequently induced, or exacerbated, by fatty food ingestion. Excessive release of, and/or hypersensitivity to, cholecystokinin (CCK) may explain the exaggerated response to lipid in patients with functional dyspepsia (FD). Thus far, plasma CCK response has been evaluated. However, stimulation of CCK1 receptors on duodenal vagal afferents occurs in a paracrine manner, suggesting that mucosal CCK concentrations are relevant to quantify. Apolipoprotein A-IV stimulates mucosal CCK release.
To investigate the hypothesis that fat-induced release of CCK and apolipoprotein A-IV (apoA-IV) is enhanced in the duodenum of FD patients.
Sixteen symptomatic FD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with intralipid 20%, 2 kcal/min, for 60 min. Symptoms were scored and blood samples were collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of CCK and apoA-IV were quantified.
Abdominal discomfort (P=0.001), nausea (P=0.05), and fullness (P=0.005) in response to duodenal lipid increased significantly only in FD patients. Following lipid infusion, the mean mucosal CCK concentration was lower in FD patients compared with HV (P<0.0001). Fasting concentrations and plasma response of CCK were comparable in FD patients and HV. Plasma apoA-IV response appeared to differ between patients and HV, whereas mucosal apoA-IV concentrations were similar.
Our results suggest excessive local release of CCK in response to duodenal lipid in FD. This likely causes exaggerated stimulation of duodenal vagal afferents, explaining dyspeptic symptom generation. The mechanisms underlying elevated mucosal CCK release warrant further investigation.
消化不良症状常因脂肪食物摄入而诱发或加重。胆囊收缩素（CCK）的过度释放和/或超敏反应可能解释了功能性消化不良（FD）患者对脂质的反应过度。到目前为止，已经评估了血浆 CCK 反应。然而，在旁分泌方式中，CCK1 受体在十二指肠迷走传入神经纤维上被刺激，这表明黏膜 CCK 浓度与定量相关。载脂蛋白 A-IV 刺激黏膜 CCK 释放。
研究 FD 患者十二指肠中脂肪诱导的 CCK 和载脂蛋白 A-IV（apoA-IV）释放增强的假设。
16 名有症状的 FD 患者和 10 名健康志愿者（HV）接受十二指肠内脂质 20%，2kcal/min 灌注 60 分钟。在脂质灌注期间每 15 分钟和停止灌注后 15 分钟对症状进行评分并采集血样，同时进行十二指肠活检。定量测定血浆和黏膜中 CCK 和 apoA-IV 的浓度。
只有 FD 患者对十二指肠脂质的反应会显著增加腹部不适（P=0.001）、恶心（P=0.05）和饱胀感（P=0.005）。与 HV 相比，FD 患者的平均黏膜 CCK 浓度较低（P<0.0001）。FD 患者和 HV 的空腹 CCK 浓度和血浆反应相当。FD 患者和 HV 之间的血浆 apoA-IV 反应似乎不同，而黏膜 apoA-IV 浓度相似。
我们的结果表明，FD 患者对十二指肠脂质的反应过度释放 CCK。这可能导致十二指肠迷走传入神经纤维的过度刺激，从而解释了消化不良症状的产生。需要进一步研究导致黏膜 CCK 释放增加的机制。
