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与斯普拉格-道利大鼠相比,由于胃迷走胆碱能张力增加,Wistar京都大鼠的胃适应性受损。

Wistar Kyoto rats have impaired gastric accommodation compared to Sprague Dawley rats due to increased gastric vagal cholinergic tone.

作者信息

Nielsen Maria Astin, Bayati Alfred, Mattsson Hillevi

机构信息

Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.

出版信息

Scand J Gastroenterol. 2006 Jul;41(7):773-81. doi: 10.1080/00365520500483215.

Abstract

OBJECTIVE

Gastric balloon distension shows that, in comparison with Sprague Dawley (SD) rats, Wistar Kyoto (WKY) rats have a decreased volume response owing to a lower accommodation rate. The aim of this study was to compare the role of the vagal cholinergic and nitrergic pathways in the accommodation reflex in these rat strains.

MATERIAL AND METHODS

The volume response to ramp-tonic gastric balloon distension was pharmacologically manipulated by using L-NAME 25 mg/kg i.v., molsidomine 20 mg/kg i.p., atropine 1 mg/kg i.v. and clonidine 0.7 mg/kg s.c.

RESULTS

Following L-NAME, the maximal volume response to distension was significantly decreased in WKY rats (0.74+/-0.11 ml versus 1.18+/-0.13 ml) whereas only a tendency to such a decrease was seen in SD rats. The NO donor molsidomine significantly increased the volume in SD rats (4.91+/-0.46 ml versus 1.81+/-0.50 ml) but only weakly in WKY rats. Atropine significantly increased the gastric volume in WKY rats (2.78+/-0.29 ml versus 1.00+/-0.17 ml) but not in SD rats. Clonidine increased the accommodation rate in the WKY rat, resulting in increased maximal volume (1.69+/-0.26 ml versus 0.65+/-0.11 ml) indicating a reduction in acetylcholine release as a consequence of stimulated presynaptic adrenergic receptors on cholinergic neurons.

CONCLUSIONS

The results indicate that WKY rats may have an increased gastric vagal cholinergic drive, which, during distension, masks the relaxing effect of NO-releasing neurons. The findings in WKY rats could be of relevance for functional dyspeptic patients with impaired gastric accommodation to meals.

摘要

目的

胃球囊扩张显示,与斯普拉格-道利(SD)大鼠相比,Wistar Kyoto(WKY)大鼠由于较低的顺应率而体积反应降低。本研究的目的是比较迷走胆碱能和一氧化氮能途径在这些大鼠品系的顺应性反射中的作用。

材料与方法

通过静脉注射25mg/kg的L-NAME、腹腔注射20mg/kg的莫西多明、静脉注射1mg/kg的阿托品和皮下注射0.7mg/kg的可乐定,对胃球囊斜坡-强直扩张的体积反应进行药理学调控。

结果

注射L-NAME后,WKY大鼠对扩张的最大体积反应显著降低(0.74±0.11ml对1.18±0.13ml),而SD大鼠仅呈现出这种降低的趋势。一氧化氮供体莫西多明显著增加了SD大鼠的体积(4.91±0.46ml对1.81±0.50ml),但对WKY大鼠的作用较弱。阿托品显著增加了WKY大鼠的胃体积(2.78±0.29ml对1.00±0.17ml),但对SD大鼠无此作用。可乐定增加了WKY大鼠的顺应率,导致最大体积增加(1.69±0.26ml对0.65±0.11ml),表明胆碱能神经元上的突触前肾上腺素能受体受刺激后乙酰胆碱释放减少。

结论

结果表明,WKY大鼠可能具有增强的胃迷走胆碱能驱动,在扩张过程中,这种驱动掩盖了一氧化氮释放神经元的舒张作用。WKY大鼠的这些发现可能与进餐时胃顺应性受损的功能性消化不良患者有关。

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