Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis.
Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis.
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DOI：
10.3748/wjg.v28.i29.3854
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发表时间：
2022-08-07
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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溃疡性结肠炎（UC）的胃肠（GI）运动障碍的机制尚未完全阐明。肠神经系统（ENS）在胃肠道运动中起着至关重要的作用。气体神经递质一氧化氮（NO）作为ENS中重要的神经递质，可能影响结肠运动。本研究采用葡聚糖硫酸钠（DSS）诱导UC大鼠模型，通过检测限速酶一氧化氮合酶（NOS）变化对UC大鼠结肠运动的影响以及ENS在UC大鼠结肠运动中的作用，探讨NO对UC大鼠的影响。目的探讨大鼠UC模型中含NOS氮能神经元中NOS表达变化与结肠运动的关系。雄性大鼠（每组8只）随机分为对照组（CG）、UC组（EG1）、UC +凝血酶衍生多肽508三氟乙酸（TP508TFA， NOS激动剂）组（EG2）和UC + ng -单甲基- l-精氨酸单醋酸酯（L-NMMA， NOS抑制剂）组（EG3）。采用不加其他处理的5.5% DSS （EG1）灌胃法诱导UC，以TP508 TFA和L-NMMA分别灌胃EG2和EG3。分别采用免疫荧光组织化学染色、Western blot和酶联免疫吸附法统计结肠氮能神经元比例的变化，记录各组疾病活跃性指数（DAI）和组织学评价。此外，利用体外器官浴系统研究了大鼠结肠圆周肌和纵向肌的收缩张力变化。与CG大鼠相比，EG1、EG2、EG3大鼠结肠肌丛（myenteric plexus， MP）内NOS阳性神经元比例、NOS相对表达量及血清和结肠组织中NOS浓度均显著升高。在UC大鼠中，激动剂和抑制剂的刺激导致EG2和EG3中每个指标的不同程度的增加或减少。EGs组大鼠发生UC时，EG1、EG2、EG3组结肠平滑肌的平均收缩张力高于CG组。与EG1相比，EG2和EG3结肠圆形肌和纵向肌的收缩幅度和平均收缩张力分别增强和减弱。因此，在UC过程中，调节mps内NOS的表达可改善肠道运动，从而有利于肠道功能的恢复。UC大鼠结肠MP中氮能神经元数量的增加导致结肠运动功能的衰减。干预NOS活性可调节结肠MP中氮能神经元的功能，预防结肠运动功能障碍。这些结果可能为缓解UC患者腹泻症状的新方法提供线索。
The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.
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DOI：
10.1124/jpet.115.228510
发表时间：
2016-02-01
影响因子：
3.5
作者：
Fornai, Matteo;Pellegrini, Carolina;Colucci, Rocchina
通讯作者：
Colucci, Rocchina
影响因子：
2.4
作者：
Lin Z;Liu Y;Zheng Q;Hu Q
通讯作者：
Hu Q
影响因子：
9.8
作者：
Higuchi, Leslie M.;Khalili, Hamed;Chan, Andrew T.;Richter, James M.;Bousvaros, Athos;Fuchs, Charles S.
通讯作者：
Fuchs, Charles S.
影响因子：
3.9
作者：
Ponder A;Long MD
通讯作者：
Long MD
影响因子：
2.3
作者：
Hoffmann, Peter;Krisam, Johannes;Gauss, Annika
通讯作者：
Gauss, Annika