Harada Tomoyuki, Fink Mitchell, Cruz Ruy J
Department of Critical Care and Emergency Medicine, Tokyo Woman's Medical University, Tokyo, Japan.
Department of Critical Care and Emergency Medicine, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
Clinics (Sao Paulo). 2018 Oct 18;73:e332. doi: 10.6061/clinics/2018/e332.
Several compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation.
Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction.
In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel.
Pre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.
几种具有与羰基共轭的烯烃键的化合物具有抗炎特性。利尿药依他尼酸（EA）就是这类化合物。在此，我们检验了依他尼酸可调节肠道操作后肠梗阻发展的假说。
将雄性C57Bl/6小鼠分为几组（每组n = 9），使用一对棉签对小肠进行手术操作（MAN组）。对照动物（CONT组）未接受任何手术干预或治疗。MAN组小鼠在术前和术后腹腔注射四剂磷酸盐缓冲盐水（PBS）、EA1（每剂1mg/kg）或EA10（每剂10mg/kg）。术后24小时给小鼠灌胃不可吸收的异硫氰酸荧光素（FITC）标记的葡聚糖，120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FD70的浓度，以此评估非吸收性FITC标记葡聚糖的胃肠转运情况。计算每只动物示踪剂的几何中心。使用半定量逆转录聚合酶链反应评估回肠固有肌层中白细胞介素-6（IL-6）和诱导型一氧化氮合酶（iNOS）转录本的表达。
在对照动物中，转运标记物的平均（±标准误）几何中心为9.89±0.47，而PBS处理动物的几何中心为4.59±0.59（与CONT组相比，p<0.05）。低剂量（1mg/kg）和高剂量（10mg/kg）依他尼酸预处理和后处理的几何中心分别为7.23±0.97和5.15±0.57。与PBS相比，依他尼酸（1mg/kg）处理显著降低了肠道操作诱导的小肠壁中IL-6和iNOS mRNA的表达。
依他尼酸预处理和后处理可改善肠梗阻，并调节肠道操作诱导的肠壁炎症。
