Harada Tomoyuki, Moore Beverley A, Yang Runkuan, Cruz Ruy J, Delude Russell L, Fink Mitchell P
Department of Critical Care Medicine, Pittsburgh, PA 15261, USA.
Surgery. 2005 Sep;138(3):530-7. doi: 10.1016/j.surg.2005.04.006.
Ethyl pyruvate (EP) improves survival, decreases proinflammatory cytokine expression, and ameliorates organ dysfunction in mice who have lethal sepsis or were subjected to hemorrhagic shock. Herein, we tested the hypothesis that treatment with EP can prevent the development of ileus after bowel manipulation, a phenomenon that is mediated by an inflammatory response in the bowel wall.
C57Bl/6 mice underwent operative manipulation of the small intestine or were subjected to a sham procedure. Some of the mice subjected to gut manipulation were pre- and post-treated with 4 doses of EP (40 or 80 mg/kg per dose), whereas others received similar volumes of the vehicle for EP. Gastrointestinal transit of a nonabsorbable marker was assessed by gavaging the mice with the tracer 24 hours after operation and assessing its concentration 90 minutes later in bowel contents from the stomach, 10 equally long segments of small intestine, the cecum, and 2 equally long segments of colon. The contractile responses of ileal circular smooth muscle to graded concentrations of bethanechol were assessed by using standard organ bath methodology. Expression of interleukin-6 and inducible nitric oxide synthase transcripts in ileal muscularis propria was assessed by using the semiquantitative reverse transcriptase-polymerase chain reaction.
In sham-operated controls, the mean (+/- SE) geometric center for the transit marker was 10.0 +/- 0.5, whereas for vehicle-treated mice subject to bowel manipulation, the value for this parameter was 3.5 +/- 0.1 (P < .05). When mice subjected to bowel manipulation were treated with several 40 mg/kg doses of EP, the geometric center was 7.3 +/- 1.0 (P < .05 vs sham-operated group). Gut manipulation impaired intestinal smooth muscle contractility in vitro and increased steady-state levels of interleukin-6 and inducible nitric oxide synthase messenger RNA. Treatment with EP ameliorated these effects of gut manipulation.
EP warrants further evaluation as a therapeutic agent to ameliorate postoperative ileus.
丙酮酸乙酯（EP）可提高致死性脓毒症小鼠或失血性休克小鼠的生存率，降低促炎细胞因子表达，并改善器官功能障碍。在此，我们检验了以下假设：EP治疗可预防肠道操作后肠梗阻的发生，这一现象由肠壁炎症反应介导。
C57Bl/6小鼠接受小肠手术操作或假手术。部分接受肠道操作的小鼠在术前和术后用4剂EP（每剂40或80 mg/kg）治疗，而其他小鼠接受等量的EP溶媒。术后24小时给小鼠灌胃示踪剂，90分钟后评估胃、10段等长小肠、盲肠和2段等长结肠内容物中示踪剂浓度，以此评估不可吸收标记物的胃肠转运。采用标准器官浴方法评估回肠环形平滑肌对不同浓度氨甲酰甲胆碱的收缩反应。采用半定量逆转录-聚合酶链反应评估回肠肌层中白细胞介素-6和诱导型一氧化氮合酶转录本的表达。
在假手术对照组中，转运标记物的平均（±标准误）几何中心为10.0±0.5，而接受肠道操作并用溶媒处理的小鼠该参数值为3.5±0.1（P<0.05）。接受肠道操作的小鼠用数剂40 mg/kg的EP治疗后，几何中心为7.3±1.0（与假手术组相比，P<0.05）。肠道操作损害了体外肠平滑肌收缩力，并增加了白细胞介素-6和诱导型一氧化氮合酶信使核糖核酸的稳态水平。EP治疗改善了肠道操作的这些影响。
EP作为改善术后肠梗阻的治疗药物值得进一步评估。
