Fukuda Hiroyuki, Chen Cindy, Mantyh Christopher, Ludwig Kirk, Pappas Theodore N, Takahashi Toku
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27705, USA.
J Surg Res. 2006 Apr;131(2):290-5. doi: 10.1016/j.jss.2005.09.018. Epub 2005 Nov 2.
BACKGROUND: Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats. MATERIALS AND METHODS: Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received 51Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT3 receptor antagonist (ondansetron; 1 mg/kg) and a 5HT4 receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation. RESULTS: Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats. CONCLUSIONS: DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine administration. DKT treatment may be useful for the patients with POI.
背景：术后肠梗阻（POI）是术后短暂的肠道运动障碍。我们之前已经表明，与单纯麻醉相比，单纯开腹手术会显著延迟胃肠道（GI）转运。开腹手术加肠道操作后，GI转运进一步延迟。大建中汤（DKT）是一种草药，在日本已用于治疗粘连性肠梗阻。我们研究了DKT是否能改善大鼠术后延迟的GI转运，无论是否给予吗啡。 材料与方法：在异氟烷麻醉下，通过开腹手术加肠道操作诱导POI。手术后立即通过灌胃给予大鼠51Cr。手术后3小时，处死大鼠，通过计算几何中心（GC）来评估GI转运。手术后通过灌胃给予DKT（120、360和1200mg/kg），无论是否给予吗啡（1mg/kg皮下注射）。在手术前给予毒蕈碱受体拮抗剂（阿托品；50μg/kg）、5HT3受体拮抗剂（昂丹司琼；1mg/kg）和5HT4受体拮抗剂（GR113,808；3mg/kg）。在手术前进行迷走神经干切断术。 结果：与单纯麻醉组（9.51±0.45）相比，开腹手术加肠道操作导致GI转运显著延迟（GC = 2.93±0.16）。360mg/kg（GC = 3.77±0.10，P < 0.01）和1200mg/kg（GC = 3.77±0.20，P < 0.01）剂量的DKT显著加速了手术诱导的延迟GI转运。昂丹司琼、GR113,808、阿托品和迷走神经干切断术消除了DKT（360mg/kg）的刺激作用。当给予吗啡时，GI转运进一步降低（GC = 1.97±0.10）。360mg/kg（GC = 2.81±0.22，P < 0.05）和1200mg/kg（GC = 2.87±0.23，P < 0.05）剂量的DKT显著改善了吗啡处理大鼠的延迟GI转运。 结论：无论是否同时给予吗啡，DKT均可加速肠道操作诱导的延迟GI转运。DKT治疗可能对POI患者有用。
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