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一种新型草药制剂可使大鼠小肠中的肠系膜传入神经对缓激肽脱敏。

A novel herbal preparation desensitizes mesenteric afferents to bradykinin in the rat small intestine.

作者信息

Mueller M H, Gong Q, Kelber O, Kasparek M S, Sibaev A, Mansmann U, Yuce B, Li Y Y, Storr M, Kreis M E

机构信息

Institute of Surgical Research, Ludwig-Maximilan's University, Munich, Germany.

出版信息

Neurogastroenterol Motil. 2009 Apr;21(4):467-76. doi: 10.1111/j.1365-2982.2008.01232.x. Epub 2008 Dec 31.

DOI:10.1111/j.1365-2982.2008.01232.x
PMID:19140959
Abstract

Herbal preparations are evolving as promising agents for the treatment of functional gastrointestinal disorders which are considered to be secondary to visceral hypersensitivity. We aimed to determine whether a new combination of six herbal extracts reduces the sensitivity of intestinal afferents in rat. Male Wistar rats (250-350 g, n = 6 per group) were gavaged with either vehicle or 2.5, 5 or 10 mL kg(-1) of STW 5-II, a herbal preparation which contains six extracts. Two hours later, animals were anaesthetized and extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum in vivo. Afferent discharge to 5-hydroxy-tryptamine (5-HT) (5, 10, 20 and 40 microg kg(-1), i.v.), luminal distension (0-60 mmHg) and bradykinin (BK) (15, 30 and 60 microg kg(-1), i.v.) was recorded. At baseline, spontaneous afferent discharge was not different following pretreatment with the various doses of STW 5-II compared with vehicle. The pressure-dependent increase in afferent discharge to intraluminal ramp distension and the dose-dependent increase in afferent firing following 5-HT were also uninfluenced by STW 5-II pretreatment. In contrast, the afferent nerve responses to 15, 30 and 60 microg kg(-1) of BK were reduced following 10 mL kg(-1) STW 5-II with peaks at 106 +/- 19, 153 +/- 22 and 156 +/- 25 imp s(-1) compared with 160 +/- 15, 228 +/- 14 and 220 +/- 16 imp s(-1) following vehicle pretreatment (mean +/- SEM, P < 0.05). Intestinal afferent sensitivity to BK which plays a prime role in nociception was reduced following STW 5-II. Thus, STW 5-II may be of therapeutic use for conditions that involve neuronal hypersensitivity and the release of BK in the intestine.

摘要

草药制剂正逐渐成为治疗功能性胃肠疾病的有前景的药物,这些疾病被认为是继发于内脏超敏反应的。我们旨在确定六种草药提取物的新组合是否能降低大鼠肠传入神经的敏感性。雄性Wistar大鼠(250 - 350克,每组n = 6)分别灌胃给予赋形剂或2.5、5或10毫升/千克的STW 5-II(一种含有六种提取物的草药制剂)。两小时后,将动物麻醉并在体内空肠近端进行细胞外多单位肠系膜传入神经记录。记录对5-羟色胺(5-HT)(5、10、20和40微克/千克,静脉注射)、肠腔扩张(0 - 60毫米汞柱)和缓激肽(BK)(15、30和60微克/千克,静脉注射)的传入放电。在基线时,与赋形剂相比,用不同剂量的STW 5-II预处理后自发传入放电没有差异。STW 5-II预处理也不影响腔内斜坡扩张时传入放电的压力依赖性增加以及5-HT后传入放电的剂量依赖性增加。相比之下,与赋形剂预处理后分别为160±15、228±14和220±16次/秒相比,10毫升/千克STW 5-II预处理后对15、30和60微克/千克BK的传入神经反应降低,峰值分别为106±19、153±22和156±25次/秒(平均值±标准误,P < 0.05)。STW 5-II后,在伤害感受中起主要作用的肠道传入神经对BK的敏感性降低。因此,STW 5-II可能对涉及神经元超敏反应和肠道中BK释放的病症具有治疗作用。

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