The ICAM‐1 antisense oligonucleotide ISIS‐3082 prevents the development of postoperative ileus in mice
The ICAM‐1 antisense oligonucleotide ISIS‐3082 prevents the development of postoperative ileus in mice
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ICAM-1 反义寡核苷酸 ISIS-3082 可预防小鼠术后肠梗阻的发生
DOI：
10.1038/sj.bjp.0706303
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发表时间：
2005
影响因子：
7.3
通讯作者：
G. Boeckxstaens
中科院分区：
文献类型：
--
作者：
F. O. The;W. de Jonge;R. Bennink;R. M. van den Wijngaard;G. Boeckxstaens
腹部手术期间的肠操作（IM）会引发炎症细胞的流入，导致术后肠梗阻。使用细胞间粘附分子 1 (ICAM-1) 和白细胞功能相关抗原 1 特异性抗体预防这种局部肌肉炎症已被证明可以缩短术后肠梗阻。然而，抗体的治疗用途具有相当大的缺点。本研究的目的是评估 ISIS-3082（一种小鼠特异性 ICAM-1 反义寡核苷酸）对小鼠术后肠梗阻的影响。在用 ICAM-1 抗体、0.1-10mg kg−1 ISIS-3082、盐水或 ISIS-8997（乱序对照反义寡核苷酸，1 和 3mg kg−1）治疗后，小鼠接受剖腹手术或剖腹手术联合 IM。术后 24 小时，使用闪烁扫描法测定 99mTC 标记的半流质膳食的胃排空情况。通过回肠肌肉整体中的髓过氧化物酶（MPO）活性评估肠道炎症。与剖腹手术相比，IM 显着减少胃排空。用 ISIS-3082 (0.1–1mg kg−1) 以及 ICAM-1 抗体 (10mg kg−1) 预处理，但不使用 ISIS-8997 或生理盐水，以剂量依赖性方式改善胃排空。随着 ISIS-3082 剂量的增加（3–10 mg kg−1），这种效应减弱。同样，ISIS-3082 (0.1–1 mg kg−1) 和 ICAM-1 抗体，但不是 ISIS-8997 或更高剂量的 ISIS-3082 (3–10 mg kg−1)，可以减少操作引起的炎症。免疫组织化学显示仅使用 ISIS-3082 即可降低 ICAM-1 表达。 ISIS-3082 预处理可通过减少操作引起的局部肠肌肉炎症来预防小鼠术后肠梗阻。我们的数据表明，使用反义寡核苷酸靶向 ICAM-1 可能代表一种预防术后肠梗阻的新治疗方法。
Intestinal manipulation (IM) during abdominal surgery triggers the influx of inflammatory cells, leading to postoperative ileus. Prevention of this local muscle inflammation, using intercellular adhesion molecule‐1 (ICAM‐1) and leukocyte function‐associated antigen‐1‐specific antibodies, has been shown to shorten postoperative ileus. However, the therapeutic use of antibodies has considerable disadvantages. The aim of the current study was to evaluate the effect of ISIS‐3082, a mouse‐specific ICAM‐1 antisense oligonucleotide, on postoperative ileus in mice. Mice underwent a laparotomy or a laparotomy combined with IM after treatment with ICAM‐1 antibodies, 0.1–10 mg kg−1 ISIS‐3082, saline or ISIS‐8997 (scrambled control antisense oligonucleotides, 1 and 3 mg kg−1). At 24 h after surgery, gastric emptying of a 99mTC labelled semi‐liquid meal was determined using scintigraphy. Intestinal inflammation was assessed by myeloperoxidase (MPO) activity in ileal muscle whole mounts. IM significantly reduced gastric emptying compared to laparotomy. Pretreatment with ISIS‐3082 (0.1–1 mg kg−1) as well as ICAM‐1 antibodies (10 mg kg−1), but not ISIS‐8997 or saline, improved gastric emptying in a dose‐dependent manner. This effect diminished with higher doses of ISIS‐3082 (3–10 mg kg−1). Similarly, ISIS‐3082 (0.1–1 mg kg−1) and ICAM‐1 antibodies, but not ISIS‐8997 or higher doses of ISIS‐3082 (3–10 mg kg−1), reduced manipulation‐induced inflammation. Immunohistochemistry showed reduction of ICAM‐1 expression with ISIS‐3082 only. ISIS‐3082 pretreatment prevents postoperative ileus in mice by reduction of manipulation‐induced local intestinal muscle inflammation. Our data suggest that targeting ICAM‐1 using antisense oligonucleotides may represent a new therapeutic approach to the prevention of postoperative ileus.
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影响因子：
4.4
作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
通讯作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
影响因子：
4.4
作者：
R. Rothlein;Michael Loran Dustin;S. D. Marlin;T. Springer
通讯作者：
R. Rothlein;Michael Loran Dustin;S. D. Marlin;T. Springer
影响因子：
29.4
作者：
Kalff, JC;Carlos, TM;Bauer, AJ
通讯作者：
Bauer, AJ
影响因子：
15.9
作者：
SMITH, CW;MARLIN, SD;ANDERSON, DC
通讯作者：
ANDERSON, DC
硫代磷酸酯寡核苷酸是人类 DNA 聚合酶和 RNase H 的抑制剂：对反义技术的影响。
影响因子：
3.6
作者：
Gao,WY;Han,FS;Storm,C;Egan,W;Cheng,YC
通讯作者：
Cheng,YC