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
선천억욱대대서유년결장을산자격치만성내장고민감적영향
Effect of inherent depression on chronic visceral hypersensitivity induced by colon acetate stimulation in neonatal rats
  • 万方数据
    北京大学学报（医学版） 북경대학학보（의학판）
    JOURNAL OF BEIJING MEDICAL UNIVERSITY(HEALTH SCIENCES)
    2015年 2期 289-294 ,共6页

    刘懿萱%张永燊%段丽萍%张璐%杨长青

    류의훤%장영신%단려평%장로%양장청

    抑郁%肠易激综合征%血清素%吲哚胺-吡咯2 ,3-双加氧酶 抑鬱%腸易激綜閤徵%血清素%吲哚胺-吡咯2 ,3-雙加氧酶
    억욱%장역격종합정%혈청소%신타알-필각2 ,3-쌍가양매
    Depression%Irritable bowel syndrome%Serotonin%Indoleamine-pyrrole 2,3-dioxygenase
    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 cingu-lated 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。
    목적：비교선천억욱대서Fawn-Hooded（FH／Wjd）여보통Sprague-Dawley（SD）대서대유년결장을산자격도치적내장고민감화뇌구격활적차이，료해선천억욱대내장민감성형성적영향급가능적중추궤제。방법：구건대서유년결장을산자격치만성내장고민감모형（ irritable bowel syndrome，IBS）。결장확장실험검측대서내장민감성；면역조직화학기술검측대서결장점막비대세포（mast cell，MC）수목화결장점막5-간색알（5-hydroxytryptamine，5-HT）적표체，이급결장점막화특정뇌구포괄전변연피질（ prelimbic cortex，PrL）화전훼구대피질（ rostral anterior cingu-lated cortex，rACC）중신타알2，3-쌍가양매（indoleamine 2，3-dioxygenase，IDO）적표체。결과：（1）대서유년결장을산자격도치복벽회측반사（ abdominal withdrawal reflex ， AWR）평분승고（ 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），차FH／Wjd IBS대서고우SD-IBS대서（2．44±0．04 vs．1．75±0．13，P＜0．05）；（2）대서유년결장을산자격도치결장점막MC수목증가（ 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／Wjd대서무론시대조조환시IBS조，결장점막 MC 수목균고우SD조（P균＜0．01）；（3）유년결장을산자격도치FH／Wjd급SD대서IBS조결장점막IDO급5-HT양성세포수균승고（P균＜0．01），차FH／Wjd대서대조급IBS조적IDO 급5-HT양성세포수고우SD 대서（대조：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， P균＜0．01）；（4）FH／Wjd-IBS대서PrL뇌구IDO표체고우SD-IBS조（49．60±4．31 vs．35．60±2．42，P ＜0．01），rACC 뇌구 IDO 표체고우 FH／Wjd 대조（45．44±1．16 vs．34．08±2．76，P＜0．01）。결론：선천억욱사대서결장을산자격후표현출경위현저적내장고민감，가능여결장MC수목화5-HT、IDO표체승고유관，제시억욱가능통과영향궤체대염증자격적반응이가중위장도공능문란。
    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). <br> 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.
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