Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats.
Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats.
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DOI：
10.1111/j.1365-2982.2011.01697.x
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发表时间：
2011-07
影响因子：
3.5
通讯作者：
Che CT
中科院分区：
文献类型：
--
作者：
Tjong YW;Ip SP;Lao L;Wu J;Fong HH;Sung JJ;Berman B;Che CT
一氧化氮（NO）参与肠易激综合征（IBS）的发病机制，但其潜在机制尚不清楚。因此，本研究的目的是探讨一氧化氮合酶（NOS）表达的作用，在远端结肠的新生儿母体分离（NMS）模型大鼠在IBS的研究。新生雄性SD大鼠随机分为NMS组和正常对照组。NMS组大鼠在出生后第2-21天每天进行3小时的母体分离。实验组和对照组分别于实验前1h腹腔注射非选择性NOS抑制剂L-NAME（100 mg/kg）、选择性神经元型NOS（nNOS）抑制剂7 NINA（10 mg/kg）、选择性诱导型NOS（iNOS）抑制剂、内皮型NOS（eNOS）抑制剂（10 mg/kg）或Vechicle（Veh;蒸馏水）。与未分离的N大鼠相比，NMS Veh大鼠的NO量显著升高。Western-blotting和实时荧光定量PCR结果显示，NMS组nNOS蛋白和mRNA表达均高于N组，而iNOS和eNOS表达无明显变化。NMS Veh大鼠对结肠扩张刺激表现出低痛阈和增加的肌电图（EMG）活动。L-NAME和7-NINA可增加NMS大鼠的痛阈压力，减弱EMG活动。此外，L-NAME和7-NINA显著降低NMS大鼠的氧化标志物丙二醛水平。NMS通过上调nNOS增加NO的产生，与活性氧相互作用，促进IBS的内脏高敏感性。
Nitric oxide (NO) is implicated in the pathogenesis of irritable bowel syndrome (IBS) but the underlying mechanism is unclear. Thus, the aim of the present study is to examine the role of NO synthase (NOS) expression in the distal colon of neonatal maternal separation (NMS) model rats employed in IBS studies. Male neonates of Sprague-Dawley rats were randomly assigned into NMS and normal control (N) groups. Rats of NMS group were subjected to 3-hr daily maternal separation on postnatal day 2–21. Rats were administrated non-selective NOS inhibitor L-NAME (100mg/kg), selective neuronal NOS (nNOS) inhibitor 7NINA (10mg/kg), selective inducible NOS (iNOS) inhibitor, endothelial NOS (eNOS) inhibitor (10mg/kg) or Vechicle (Veh; distilled water) intraperitoneally 1 hour prior to the experiment for the test and control groups, respectively. The amount of NO was significantly higher in the NMS Veh rats compared with unseparated N rats. Western-blotting and real-time quantitative PCR studies showed that protein and mRNA expression of nNOS were higher in the NMS group than that in the N rats; whereas no significant change in iNOS and eNOS was found in either groups. NMS Veh rats showed low pain threshold and increased electromyogram (EMG) activity in response to colonic distension stimuli. L-NAME and 7NINA increased pain threshold pressure and attenuated EMG activity in the NMS rats. In addition, L-NAME and 7-NINA substantially reduced oxidative marker malondialdehyde level in NMS rats. NMS increased the NO generation by nNOS upregulation that interact with reactive oxygen species contributing to the visceral hypersensitivity in IBS.
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影响因子：
9.8
作者：
Choung, Rok Seon;Locke, G. Richard, III;Zinsmeister, Alan R.;Schleck, Cathy D.;Talley, Nicholas J.
通讯作者：
Talley, Nicholas J.
影响因子：
24.5
作者：
Collins, SM;Piche, T;Rampal, P
通讯作者：
Rampal, P
DOI：
10.1152/ajpgi.00400.2006
发表时间：
2007-03-01
影响因子：
4.5
作者：
Ren, Tian-Hua;Wu, Justin;Sung, Joseph J. Y.
通讯作者：
Sung, Joseph J. Y.
影响因子：
9.3
作者：
Benabdallah, Hassiba;Messaoudi, Dahla;Gharzouli, Kamel
通讯作者：
Gharzouli, Kamel
影响因子：
24.5
作者：
Bengtson, M. -B.;Ronning, T.;Harris, J. R.
通讯作者：
Harris, J. R.