Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Tohoku J Exp Med. 2013 Aug;230(4):197-204. doi: 10.1620/tjem.230.197.
Japanese herbal medicine, also known as Kampo, is used for various diseases in Japan. One of those medicines, Dai-Kenchu-To (DKT), is considered clinically effective for adhesive bowel obstruction and chronic constipation. Although scientific evidence of DKT to improve adhesive bowel obstruction was shown in several previous reports, mechanism of DKT to improve constipation remains unknown. Our aim was to study the effect of intragastric DKT on colonic motility and defecation, and the involvement of various receptors in DKT-induced colonic contractions. Five beagle dogs were instructed with serosal strain-gauge force transducers to measure circular muscle activity at the proximal, middle, and distal colon. Dogs are suitable for a present study to administer the drugs repeatedly to the same individual and look at its effect on colonic motility. We studied the effects of DKT (2.5 or 5 g) administered into the stomach on colonic motility. Muscarinic receptor antagonist atropine, nicotinic receptor antagonist hexamthonium, or 5-hydroxytryptamine-3 receptor antagonist ondansetron was injected intravenously 10 min before DKT administration. Capsazepine, an antagonist to transient receptor potential cation channel subfamily V member 1 (TRPV1), was administered into the stomach 5 min before DKT administration. Intragastric DKT (2.5 or 5 g) induced colonic contractions within 10 min after administration but did not induce defecation. Pretreatment with atropine, hexamthonium, ondansetron, or capsazepine inhibited DKT-induced colonic contractions. These results indicate that orally administered DKT stimulates colonic motility via TRPV1, muscarinic, nicotinic, and 5-hydroxytryptamine-3 receptors, thereby providing scientific support for the efficacy of oral DKT in chronic constipation.
日本草药医学,也被称为汉方药,在日本被用于各种疾病。其中一种药物,大建中汤(DKT),被认为对粘连性肠梗阻和慢性便秘具有临床疗效。尽管先前的一些报告已经显示了 DKT 改善粘连性肠梗阻的科学证据,但 DKT 改善便秘的机制尚不清楚。我们的目的是研究胃内给予 DKT 对结肠动力和排便的影响,以及 DKT 诱导的结肠收缩中涉及的各种受体。我们使用肠浆膜应变计力换能器指导五只比格犬,以测量近端、中段和远端结肠的环形肌活动。犬适合用于本研究,因为可以对同一动物重复给药并观察其对结肠动力的影响。我们研究了胃内给予 DKT(2.5 或 5 g)对结肠动力的影响。在给予 DKT 之前 10 分钟,静脉内给予毒蕈碱受体拮抗剂阿托品、烟碱受体拮抗剂六烃季铵或 5-羟色胺 3 受体拮抗剂昂丹司琼。给予 DKT 前 5 分钟,将辣椒素(瞬时受体电位阳离子通道亚家族 V 成员 1(TRPV1)的拮抗剂)给予胃内。胃内给予 DKT(2.5 或 5 g)可在给药后 10 分钟内引起结肠收缩,但不会引起排便。阿托品、六烃季铵、昂丹司琼或辣椒素预处理抑制了 DKT 诱导的结肠收缩。这些结果表明,口服给予 DKT 通过 TRPV1、毒蕈碱、烟碱和 5-羟色胺 3 受体刺激结肠动力,从而为口服 DKT 治疗慢性便秘的疗效提供了科学依据。