Mourad Fadi H, Barada Kassem A, Bou Rached Nadine A, Khoury Carmen I, Saadé Nayef E, Nassar Camille F
American University of Beirut Medical Centre, PO Box 113-6044, Hamra 110-32090, Beirut, Lebanon.
Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G262-8. doi: 10.1152/ajpgi.00271.2005. Epub 2005 Aug 25.
Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide (VIP) antagonism, 5) nitric oxide (NO) synthase (NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT(3) and 5-HT(4)) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) microl x min(-1) x g dry intestinal wt(-1), respectively [P < 0.0002 compared with sham rats at 61 (SD 6.5) microl x min(-1) x g dry intestinal wt(-1)]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 (SD 13) and 44 (SD 14) microl x min(-1) x g dry intestinal wt(-1) (P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) microl x min(-1) x g dry intestinal wt(-1) (P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) microl x min(-1) x g dry intestinal wt(-1), respectively. 5-HT(3) and 5-HT(4) receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.
溃疡性结肠炎患者及实验性结肠炎动物模型中均有小肠吸收功能受损的描述。这种功能障碍的病理生理学尚未阐明。本研究的目的是探讨化学性结肠炎对空肠液体吸收的影响，并确定肠神经系统及一些假定神经递质的作用。在碘乙酰胺诱导的结肠炎大鼠模型中，采用体内单通道灌注技术评估空肠净液体吸收。研究了1）河豚毒素（TTX）、2）苯扎氯铵（BAC）、3）辣椒素、4）血管活性肠肽（VIP）拮抗、5）一氧化氮（NO）合酶（NOS）抑制以及6）5-羟色胺3型和4型（5-HT(3)和5-HT(4)）受体拮抗对液体运动变化的影响。结肠炎诱导后2天和4天，空肠净液体吸收显著降低：分别为26（标准差14）和28（标准差19）微升×分钟(-1)×克干肠重(-1) [与假手术大鼠的61（标准差6.5）微升×分钟(-1)×克干肠重(-1)相比，P < 0.0002]。空肠切片未见明显组织学变化。TTX和BAC可逆转液体吸收的这种降低：分别为54（标准差13）和44（标准差14）微升×分钟(-1)×克干肠重(-1)（与结肠炎相比，P分别为0.0005和0.019）。辣椒素敏感的初级传入纤维的切断有部分作用：45（标准差5）微升×分钟(-1)×克干肠重(-1)（与结肠炎和假手术相比，P分别为0.001和0.003）。组成型和神经元型NOS抑制以及VIP拮抗使空肠净液体吸收恢复至正常水平：分别为66（标准差19）、61（标准差5）和56（标准差14）微升×分钟(-1)×克干肠重(-1)。5-HT(3)和5-HT(4)受体拮抗无作用。化学性结肠炎与空肠净液体吸收显著降低有关。这种降低是由神经介导的，涉及VIP和NO相关机制。
