■我们先前显示了肠易激综合征(IBS)患者应用结肠粘膜活检上清液后的肠神经激活。问题仍然是这是针对特定区域的还是普遍的敏感化。我们测试了IBS腹泻患者(IBS-D)的大肠和小肠区域上清液的神经激活特性,与肥大细胞增多症患者腹泻(MC-D)或非IBS/非MC患者的神经激活特性-投诉。MC-D患者被纳入到来自已确定的患者的测试样本中,严重的肥大细胞疾病,因为建议肥大细胞在IBS中起作用。
■使用电压敏感染料成像记录来自IBS-D的粘膜活检上清液的影响,MC-D,和非IBS/非MC对豚鼠粘膜下神经元的影响。在所有样品中测量肥大细胞密度和组胺浓度。
■IBS-D(十二指肠和结肠,近端和远端,分别为49.3;50.5;63.7;71.9)与非IBS/非MC(十二指肠和结肠,近端和远端,8.7;4.9;6.9;5.4)或MC-D上清液(十二指肠和结肠,近端和远端,9.4;11.9;0.0;7.9)。MC-D和非IBS/非MC上清液的神经激活是相当的(p>0.05)。肥大细胞密度或组胺浓度在IBS-D之间没有差异,MC-D,和非IBS/非MC样品。
■活检上清液激活神经是IBS的标志,发生在整个肠道,与肥大细胞密度或组胺浓度无关。至少同样重要的是我们的发现,胃肠道主诉本身与活检上清液诱导的神经激活无关,这进一步强调了IBS中神经行为改变的相关性。
UNASSIGNED: We previously showed enteric nerve activation after application of colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS). The question remains whether this is a region-specific or a generalized sensitization. We tested the nerve-activating properties of supernatants from large and small intestinal regions of IBS patients with diarrhea (IBS-D) in comparison to those from mastocytosis patients with diarrhea (MC-D) or non-IBS/non-MC patients with GI-complaints. MC-D patients were included to test samples from patients with an established, severe mast cell disorder, because mast cells are suggested to play a role in IBS.
UNASSIGNED: Voltage-sensitive dye imaging was used to record the effects of mucosal biopsy supernatants from IBS-D, MC-D, and non-IBS/non-MC on guinea pig submucous neurons. Mast cell density and histamine concentrations were measured in all samples.
UNASSIGNED: The median neuroindex (spike frequency × % responding neurons in Hz × %) was significantly (all p < 0.001) increased for IBS-D (duodenum and colon, proximal and distal each, 49.3; 50.5; 63.7; 71.9, respectively) compared to non-IBS/non-MC (duodenum and colon, proximal and distal each, 8.7; 4.9; 6.9; 5.4, respectively) or MC-D supernatants (duodenum and colon, proximal and distal each, 9.4; 11.9; 0.0; 7.9, respectively). Nerve activation by MC-D and non-IBS/non-MC supernatants was comparable (p>0.05). Mast cell density or histamine concentrations were not different between IBS-D, MC-D, and non-IBS/non-MC samples.
UNASSIGNED: Nerve activation by biopsy supernatants is an IBS hallmark that occurs throughout the gut, unrelated to mast cell density or histamine concentration. At least as important is our finding that GI complaints per se were not associated with biopsy supernatant-induced nerve activation, which further stresses the relevance of altered nerve behavior in IBS.