先天抑郁对大鼠幼年结肠乙酸刺激致慢性内脏高敏感的影响

目的：比较先天抑郁大鼠Fawn-Hooded（FH/Wjd）与普通Sprague-Dawley（SD）大鼠对幼年结肠乙酸刺激导致的内脏高敏感和脑区激活的差异，了解先天抑郁对内脏敏感性形成的影响及可能的中枢机制。方法：构建大鼠幼年结肠乙酸刺激致慢性内脏高敏感模型（irritable bowel syndrome，IBS）。结肠扩张实验检测大鼠内脏敏感性；免疫组织化学技术检测大鼠结肠黏膜肥大细胞（mast cell，MC）数目和 结肠黏膜5-羟色胺（5-hydroxytryptamine，5-HT）的表达，以及结肠黏膜和特定脑区包括前边缘皮质（prelimbic cortex，PrL）和前喙扣带皮质（rostral anterior cingulated cortex，rACC）中吲哚胺2,3-双加氧酶（indoleamine 2,3 dioxygenase，IDO）的表达。结果：（1）大鼠幼年结肠乙酸刺激导致腹壁回测反射（abdominal withdrawal reflex , AWR）评分升高（FH/Wjd：2.44±0.04 vs.1.96±0.07，P<0.05；SD：1.75±0.13 vs.1.32±0.05，P<0.05），且FH/Wjd IBS大鼠高于SD-IBS大鼠（2.44±0.04 vs.1.75±0.13，P<0.05）；（2）大鼠幼年结肠乙酸刺激导致结肠黏膜MC数目增加（FH/Wjd：43.24±1.72 vs. 24.92±1.38，P< 0.01；SD：23.80±1.28 vs. 14.24±0.92，P < 0.01），FH/Wjd大鼠无论是对照组还是IBS 组，结肠黏膜 MC 数目均高于SD组（P均 < 0.01）；（3）幼年结肠乙酸刺激导致FH/Wjd及SD大鼠IBS组结肠黏膜 IDO 及5-HT阳性细胞数均升高（P均<0.01），且FH/Wjd 大鼠对照及IBS组的IDO 及5-HT阳性细胞数高于SD 大鼠（对照：IDO，24.64 ± 2.22 vs. 15.52 ± 1.39；5 HT，21.32 ± 1.26 vs. 12.72 ± 1.12。 IBS：IDO，44.92 ± 2.31 vs. 20.85 ± 1.72；5-HT，31.84 ± 1.57 vs. 19.65 ± 1.09， P均<0.01）；（4）FH/Wjd-IBS大鼠PrL 脑区IDO表达高于SD-IBS 组（49.60 ± 4.31 vs. 35.60 ± 2.42，P <0.01），rACC脑区IDO表达高于FH/Wjd对照（45.44 ± 1.16 vs. 34.08 ± 2.76，P<0.01）。结论：先天抑郁使大鼠结肠乙酸刺激后表现出更为显著的内脏高敏感，可能与结肠MC数目和5-HT、IDO表达升高有关，提示抑郁可能通过影响机体对炎症刺激的反应而加重胃肠道功能紊乱。

Effect of inherent depression on chronic visceral hypersensitivity induced by colon acetate stimulation in neonatal rats

Objective:To explore the effect of inherent depression on chronic visceral hypersensitivity. The differences of visceral sensitivity, colitis, and brain activation between Fawn-Hooded ( FH/Wjd) and Sprague-Dawley( SD) rats were identified after neonatal colon acetate stimulation.Methods:The specific pathogen free Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were used to establish irritable bowel syndrome (IBS) model.The visceral sensitivity was measured by colorectal distension (CRD). The expression of 5-hydroxytryptamine (5-HT), mast cell (MC), indoleamine 2,3-dioxygenase (IDO) in colon and IDO in specific cerebral regions were detected through immunohistochemistry.Results:Ab-dominal withdrawal reflex ( AWR) scores showed that visceral sensitivity of acetate-enema groups was sig-nificantly higher than that of saline-enema groups ( FH/Wjd:2.44 ±0.04 vs.1.96 ±0.07, P<0.05;SD:1.75 ±0.13 vs.1.32 ±0.05, P<0.05).Furthermore, FH/Wjd rats of IBS group scored signifi-cantly higher than SD rats of IBS group (2.44 ±0.04 vs.1.75 ±0.13, P<0.05).The MC amounts of both SD and FH/Wjd IBS group rats were significantly more than those of their control groups ( FH/Wjd:43.24 ±1.72 vs.24.92 ±1.38, P <0.01.SD:23.80 ±1.28 vs.14.24 ±0.92, P <0.01).
Besides, the MC amounts of control and IBS group of FH/Wjd rats were significantly more than that of SD IBS group rats ( P<0 .01 ) .The IDO and 5-HT positive cells in colonic mucosa of IBS group of both SD and FH/Wjd rats were significantly more than those of their control groups, respectively(P <0.01). The IDO, 5-HT positive cells in colonic mucosa of both control and IBS group of FH/Wjd rats were significantly more than those of both control and IBS group of SD rats ( control:IDO,24.64 ±2.22 vs. 15.52 ±1.39;5-HT,21.32 ±1.26 vs.12.72 ±1.12.IBS: IDO,44.92 ±2.31 vs.20.85 ±1.72;5-HT, 31.84 ±1.57 vs.19.65 ±1.09.P <0.01).The expression of IDO in prelimbic cortex (PrL) areas of FH/Wjd IBS rats was significantly higher than that of IBS group of SD rats (49.60 ±4.31 vs. 35.60 ±2.42, P <0.01) , and the expression of IDO in rostral anterior cingulate cortex ( rACC) areas of FH/Wjd IBS rats was significantly more than that of FH/Wjd control rats (45.44 ±1.16 vs.34.08 ± 2.76, P <0.01) .Conclusion:Inherent depressive FH/Wjd rats were more sensitive to neonatal colon acetate stimulation, presenting as visceral hypersensitivity which maybe associated with increased MC amounts and over-expression of 5-HT and IDO in colon, suggesting that depression disorder may aggra-vate functional disturbance of gastrointestinal tract by regulating the response to inflammatory stimulation.