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右旋糖酐硫酸钠诱导的胃肠道损伤进一步加重加兰他敏对实验猪胃肌电活动的影响。

Dextran Sodium Sulphate-Induced Gastrointestinal Injury Further Aggravates the Impact of Galantamine on the Gastric Myoelectric Activity in Experimental Pigs.

作者信息

Bures Jan, Tacheci Ilja, Kvetina Jaroslav, Radochova Vera, Kohoutova Darina, Valis Martin, Rejchrt Stanislav, Knoblochova Veronika, Zdarova Karasova Jana

机构信息

2nd Department of Internal Medicine-Gastroenterology, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital, 500 03 Hradec Kralove, Czech Republic.

Animal Laboratory, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic.

出版信息

Pharmaceuticals (Basel). 2021 Jun 18;14(6):590. doi: 10.3390/ph14060590.

Abstract

Galantamine has been used as a treatment for Alzheimer disease. It has a unique, dual mode of action (inhibitor of acetylcholinesterase and allosteric modulator of nicotinic acetylcholine receptors). Nausea (in about 20%), vomiting (10%) and diarrhoea (5-7%) are the most common side effects. The aim of this study was to assess the effect of galantamine on porcine gastric myoelectric activity without (Group A) and with (Group B) dextran sodium sulphate (DSS)-induced gastrointestinal injury. Galantamine hydrobromide was administrated to twelve pigs as a single intragastric dose (24 mg). Gastric myoelectric activity was investigated by electrogastrography (EGG). Basal (15 min before galantamine administration) and study recordings after galantamine administration (300 min) were evaluated using a running spectral analysis. Results were expressed as dominant frequency of gastric slow waves and power analysis (areas of amplitudes). Altogether, 3780 one-minute EGG recordings were evaluated. In Group A, power was steady from basal values for 180 min, then gradually decreased till 270 min ( = 0.007). In Group B, there was a rapid gradual fall from basal values to those after 120 min ( = 0.007) till 300 min ( ˂ 0.001). In conclusion, galantamine alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of galantamine-associated dyspepsia in humans. DSS caused further profound decrease of EGG power. That may indicate that underlying inflammatory, ischaemic or NSAIDs-induced condition of the intestine in humans can have aggravated the effect of galantamine on gastric myoelectric activity.

摘要

加兰他敏已被用作治疗阿尔茨海默病的药物。它具有独特的双重作用模式(乙酰胆碱酯酶抑制剂和烟碱型乙酰胆碱受体变构调节剂)。恶心(约20%)、呕吐(10%)和腹泻(5 - 7%)是最常见的副作用。本研究的目的是评估加兰他敏对猪胃肌电活动的影响,分为无(A组)和有(B组)葡聚糖硫酸钠(DSS)诱导的胃肠道损伤两种情况。将氢溴酸加兰他敏以单次胃内给药剂量(24 mg)给予12头猪。通过胃电图(EGG)研究胃肌电活动。使用连续频谱分析评估基础状态(加兰他敏给药前15分钟)和加兰他敏给药后(300分钟)的研究记录。结果以胃慢波的主导频率和功率分析(振幅面积)表示。总共评估了3780份1分钟的EGG记录。在A组中,功率从基础值稳定180分钟,然后逐渐下降直至270分钟(P = 0.007)。在B组中,从基础值迅速逐渐下降至120分钟后的水平(P = 0.007),直至300分钟(P ˂ 0.001)。总之,单独使用加兰他敏对通过胃功率评估的猪肌电活动显示出不利影响。这可能是人类中加兰他敏相关消化不良的一个合理原因。DSS导致EGG功率进一步显著下降。这可能表明人类潜在的炎症、缺血或非甾体抗炎药诱导的肠道状况可能加重了加兰他敏对胃肌电活动的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069a/8234489/4c9b9b7795a7/pharmaceuticals-14-00590-g001.jpg

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