背景:内脏超敏反应和心理表现是肠易激综合征(IBS)的主要病理生理机制。先前的研究发现,胆囊收缩素(CCK)可以增强结肠运动,5-羟色胺转运体(SERT)是一种对5-羟色胺具有高亲和力的跨膜转运蛋白,能迅速再摄取5-羟色胺,进而调节其作用时间和强度。我们推测SERT和CCK可能通过影响内脏敏感性和脑-肠轴在腹泻型IBS(IBS-D)的发病机制中发挥作用。
目的:确定使用罗马IV标准诊断的IBS-D患者的SERT和CCK水平,并分析其与腹痛的关系。内脏过敏和心理表现。
方法:本研究收集了2017年9月至2018年4月中日友好医院40例IBS-D患者和18例健康对照者的数据。腹痛的严重程度,在IBS-D患者和健康对照中评估内脏敏感性和心理表现,评估血浆和结肠黏膜中SERT和CCK的水平,并分析了它们之间的相关性。
结果:初始感觉阈值存在显着差异(31.00±8.41mLvs52.22±8.09mL,P<0.001),排便感觉阈值(51.75±13.57mLvs89.44±8.73mL,P<0.001)和最大容许阈值(97.25±23.64mLvs171.11±20.83mL,两组之间P<0.001)。与健康对照组相比,IBS-D患者的焦虑(7.78±2.62vs2.89±1.02,P<0.001)和抑郁(6.38±2.43vs2.06±0.73,P<0.001)症状更严重。两组粘膜CCK(2.29±0.30vs1.66±0.17,P<0.001)和SERT(1.90±0.51vs3.03±0.23,P<0.001)也存在显着差异。疼痛评分与粘膜CCK呈显著正相关(r=0.96、0.93、0.94,P<0.001)。焦虑之间呈显著负相关(r=-0.98;P<0.001),抑郁(r=-0.99;P<0.001),疼痛评估(r=-0.96,-0.93,-0.95,P<0.001)和粘膜SERT。
结论:IBS-D患者有心身疾病和内脏高敏感性。SERT和CCK可能通过调节脑-肠轴和影响内脏敏感性参与IBS-D的发病。这为识别更具体和有效的治疗靶标提供了新的潜在方法。
BACKGROUND: Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome (IBS). Previous studies have found that cholecystokinin (CCK) can enhance colon movement and that serotonin transporter (SERT) is a transmembrane transport protein with high affinity for 5-hydroxytryptamine, which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity. We speculate that SERT and CCK might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D) by affecting visceral sensitivity and the brain-gut axis.
OBJECTIVE: To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain, visceral hypersensitivity and psychological performance.
METHODS: This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls. The severity of abdominal pain, visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls, the levels of SERT and CCK in plasma and colonic mucosa were evaluated, and the correlations between them were analyzed.
RESULTS: There were significant differences in the initial sensation threshold (31.00 ± 8.41 mL vs 52.22 ± 8.09 mL, P < 0.001), defecating sensation threshold (51.75 ± 13.57 mL vs 89.44 ± 8.73 mL, P < 0.001) and maximum tolerable threshold (97.25 ± 23.64 mL vs 171.11 ± 20.83 mL, P < 0.001) between the two groups. IBS-D patients had more severe anxiety (7.78 ± 2.62 vs 2.89 ± 1.02, P < 0.001) and depressive (6.38 ± 2.43 vs 2.06 ± 0.73, P < 0.001) symptoms than healthy controls. Significant differences were also found in mucosal CCK (2.29 ± 0.30 vs 1.66 ± 0.17, P < 0.001) and SERT (1.90 ± 0.51 vs 3.03 ± 0.23, P < 0.001) between the two groups. There was a significant positive correlation between pain scores and mucosal CCK (r = 0.96, 0.93, 0.94, P < 0.001). Significant negative correlations between anxiety (r = -0.98; P < 0.001), depression (r = -0.99; P < 0.001), pain evaluation (r = -0.96, -0.93, -0.95, P < 0.001) and mucosal SERT were observed.
CONCLUSIONS: IBS-D patients had psychosomatic disorders and visceral hypersensitivity. SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the brain-gut axis and affecting visceral sensitivity. This provides a new potential method for identifying a more specific and effective therapeutic target.