El-Salhy Magdy, Hatlebakk Jan Gunnar, Hausken Trygve
Magdy El-Salhy, Jan Gunnar Hatlebakk, Trygve Hausken, Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.
World J Gastroenterol. 2015 Aug 28;21(32):9577-87. doi: 10.3748/wjg.v21.i32.9577.
To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome (IBS) is associated with abnormalities in stem cell differentiation.
The study sample comprised 203 patients with IBS (180 females and 23 males with a mean age of 36 years) and a control group of 86 healthy subjects without gastrointestinal complaints (77 females and 9 males with a mean age of 38 years). The patients included 80 with mostly diarrhoea (IBS-D), 47 with both diarrhoea and constipation (IBS-M), and 76 with mostly constipation (IBS-C). Both the patients and controls underwent gastroscopy and four biopsy samples were taken from the descending part of the duodenum, proximal to the papilla of Vater. The biopsy samples were sectioned and immunostained for Musashi 1 (Msi-1), neurogenin 3 (NEUROG3), secretin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), somatostatin and serotonin. Immunostaining was performed with an ultraView Universal DAB Detection Kit (v1.02.0018, Venata Medical Systems, Basal, Switzerland) using the BenchMark Ultra immunohistochemistry/in situ hybridization staining module (Venata Medical Systems). Endocrine cell densities were quantified by computerized image analysis using the Olympus cellSens imaging program.
The densities of Msi-1 and NEUROG3 cells were significantly lower in IBS patients, regardless of the subtype, than in the controls (77 ± 17 vs 8 ± 2; P = 0.0001, and 351 ± 33 vs 103 ± 22; P = 0.00002, respectively). Furthermore, the densities of secretin, and CCK cells were significantly lower in patients with diarrhoea as the predominant IBS symptom (IBS-D) than in the controls (161 ± 11 vs 88 ± 8; P = 0.00007, and 325 ± 41 vs 118 ± 10; P = 0.00006, respectively), but not in patients with constipation as the predominant IBS symptom (IBS-C) or those with both diarrhoea and constipation (IBS-M). The GIP cell density was significantly reduced in both IBS-D (152 ± 12 vs 82 ± 7; P = 0.00003), and IBS-C (152 ± 12 vs 107 ± 8; P = 0.01), but not in IBS-M. The densities of somatostatin cells in the controls and the IBS-total, IBS-D, IBS-M and IBS-C patients were 81 ± 8, 28 ± 3, 20 ± 4, 37 ± 5 and 28 ± 4 cells/mm(2) epithelium, respectively. The density of somatostatin cells was lower in IBS-total, IBS-D, IBS-M and IBS-C patients than in the controls (P = 0.00009, 0.00006, 0.009 and 0.00008, respectively). The density of serotonin cells did not differ between IBS patients and controls.
The reduction in duodenal endocrine cells in IBS patients found in this study is probably attributable to the reduction in cells expressing Msi-1 and NEUROG3.
确定肠易激综合征（IBS）患者十二指肠内分泌细胞密度降低是否与干细胞分化异常有关。
研究样本包括203例IBS患者（180例女性和23例男性，平均年龄36岁）和86例无胃肠道不适的健康对照者（77例女性和9例男性，平均年龄38岁）。患者包括80例以腹泻为主（IBS-D）、47例腹泻与便秘并存（IBS-M）和76例以便秘为主（IBS-C）。患者和对照者均接受胃镜检查，并从十二指肠降部距Vater壶腹近端取4块活检样本。将活检样本切片，用抗Musashi 1（Msi-1）、神经生成素3（NEUROG3）、促胰液素、胆囊收缩素（CCK）、胃抑制肽（GIP）、生长抑素和5-羟色胺进行免疫染色。使用BenchMark Ultra免疫组织化学/原位杂交染色模块（Venata Medical Systems），采用UltraView Universal DAB检测试剂盒（v1.02.0018，Venata Medical Systems，瑞士巴塞尔）进行免疫染色。使用Olympus cellSens成像程序通过计算机图像分析对内分泌细胞密度进行定量。
无论亚型如何，IBS患者中Msi-1和NEUROG3细胞的密度均显著低于对照组（分别为77±17对8±2；P = 0.0001，以及351±33对103±22；P = 0.00002）。此外，以腹泻为主要IBS症状（IBS-D）的患者中促胰液素和CCK细胞的密度显著低于对照组（分别为161±11对88±8；P = 0.00007，以及325±41对118±10；P = 0.00006），但以便秘为主要IBS症状（IBS-C）或腹泻与便秘并存（IBS-M）的患者中则不然。GIP细胞密度在IBS-D（152±12对82±7；P = 0.00003）和IBS-C（152±12对107±8；P = 0.01）中均显著降低，但在IBS-M中未降低。对照组以及IBS总患者、IBS-D、IBS-M和IBS-C患者中生长抑素细胞的密度分别为81±8、28±3、20±4、37±5和28±4个细胞/mm²上皮。IBS总患者、IBS-D、IBS-M和IBS-C患者中生长抑素细胞的密度低于对照组（分别为P = 0.00009, 0.00006, 0.009和0.00008）。IBS患者和对照组之间5-羟色胺细胞的密度无差异。
本研究中发现IBS患者十二指肠内分泌细胞减少可能归因于表达Msi-1和NEUROG3的细胞减少。
