Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS Gene Expression
Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS Gene Expression
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DOI：
10.1007/s10753-017-0576-7
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发表时间：
2017-05
期刊：
影响因子：
5.1
通讯作者：
T. Mihara;S. Mikawa;N. Kaji;M. Endo;T. Oikawa;Jan Tong-Rong;H. Ozaki;M. Hori
中科院分区：
文献类型：
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作者：
T. Mihara;S. Mikawa;N. Kaji;M. Endo;T. Oikawa;Jan Tong-Rong;H. Ozaki;M. Hori
术后肠梗阻是腹部手术后常见的并发症。炎症胃肠道巨噬细胞产生的一氧化氮在术后肠梗阻的发病机制中起重要作用。檀香木，从木兰树皮中提取，是一种具有双酚结构的天然化合物。在本研究中，我们研究了和诺平对术后肠梗阻的影响，并讨论了其作用部位。采用外科肠操作法建立术后肠梗阻模型。在肠道操作之前和之后1小时，对小鼠施用和诺明（10 mg kg−1，口服）。在术后肠梗阻模型小鼠中测量胃肠道传输、白细胞浸润和炎症介质的信使RNA（mRNA）表达。我们还研究了和厚朴在脂多糖刺激的腹腔巨噬细胞中的炎症作用。术后肠梗阻模型小鼠的胃肠传输延迟，和诺明可恢复受损的传输。和厚朴能显著抑制术后肠梗阻模型小鼠回肠肌层白细胞浸润和促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1 β和白细胞介素-6）及诱导型一氧化氮合酶的上调。在由脂多糖激活的腹腔巨噬细胞中，和厚朴酚显著抑制促炎细胞因子和诱导型一氧化氮合酶的mRNA表达上调。和诺平能显著改善术后肠梗阻患者的胃肠动力障碍，抑制肠道炎症反应。此外，和厚朴酚被认为对巨噬细胞有影响，即抑制促炎细胞因子和诱导型一氧化氮合酶的mRNA表达。总的来说，honoklastine代表了一种潜在的新型治疗药物，用于术后肠梗阻。
Postoperative ileus is a common complication after intra-abdominal surgery. Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from the bark ofMagnoliaspp., is a natural compound with a biphenolic structure. In the present study, we examined the effect of honokiol on postoperative ileus and discussed its site of action. Postoperative ileus model mice were generated by surgical intestinal manipulation. Mice were administered honokiol (10 mg kg−1,per os) 1 h before and after intestinal manipulation. Gastrointestinal transit, leukocyte infiltration, and messenger RNA (mRNA) expression of inflammatory mediators were measured in postoperative ileus model mice with or without honokiol. We also investigated the inflammatory effect of honokiol in lipopolysaccharide-stimulated peritoneal macrophages. Gastrointestinal transit was delayed in postoperative ileus model mice and honokiol recovered the impaired transit. Honokiol significantly inhibited leukocyte infiltration and upregulation of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and inducible nitric oxide synthase in the ileal muscle layer of postoperative ileus model mice. In peritoneal macrophages activated by lipopolysaccharide, honokiol significantly inhibited the upregulated mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Honokiol significantly recovered gastrointestinal dysmotility and inhibited intestinal inflammation in postoperative ileus. Moreover, honokiol was suggested to have effects on macrophages, namely, inhibiting mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Taken together, honokiol represents a potential novel therapeutic agent for postoperative ileus.