Usefulness of chymase inhibitor for prevention of abdominal adhesion in rats

[Speaker] Maiko Ozeki:1
[Co-author] Denan Jin:2, Yuta Miyaoka:1, Fumitoshi Hirokawa:1, Michihiro Hayashi:1, Keitaro Tanaka:1, Kazuhisa Uchiyama:1, Shinji Takai:2
1:Department of General and Gastroenterological Surgery, Osaka medical college, Japan, 2:Department of Innovative Medicine, Graduate school of Medicine, Osaka medical college, Japan

Postoperative abdominal adhesions are significant problems that lead to chronic abdominal pain, intestinal obstruction, infertility and re-operation. Seprafilm, a sodium hyaluronate/carboxymethylcellulose absorbable barrier, has been widely used to prevent adhesions after abdominal surgery. However, seprafilm is seldom used in laparoscopic surgery because of its tendency to break apart when inserted into the abdominal cavity through a trocar. Therefore, a strategy to overcome this problem remains necessary. We have reported that mast cell chymase is closely associated with adhesion formation. Here, we compared the preventive effects of a chymase inhibitor with that of seprafilm in a novel rat adhesion model that has shown high reproducibility for adhesion formation.

A cotton pad (10 × 20 mm) was soaked with 1 N NaOH and then placed on the surface of the cecum for 1 minute to induce abdominal adhesion in rats. Rats were divided into four groups: normal, alkali-induced adhesion (vehicle), and alkali-induced adhesion treated with chymase inhibitor or seprafilm. To evaluate the preventive effects of chymase inhibitor and seprafilm, the chymase inhibitor 10 μM Suc-Val-Pro-Phep(OPh)2 was injected into the abdomen immediately after alkali-induced injury or seprafilm was applied to the injured cecum. Adhesion scores were evaluated 2 weeks after alkali-induced injury, and adhesion-related factors in the cecum were analyzed 1 day after alkali-induced injury.

Adhesion score was 3.83 ± 0.16 in the vehicle group (n=6), but decreased significantly to 2.1 ± 0.31 and 2.1 ± 0.31 after treatment with chymase inhibitor and seprafilm, respectively. Significant augmentations of chymase activity and mast cell number were observed in the vehicle group at 14 days after alkali injury, but they were attenuated by chymase inhibitor. On the other hand, myeloperoxidase mRNA levels, which indicate recruitment of inflammatory cells, were markedly increased on day 1, but were substantially decreased by seprafilm.

The action mechanisms of chymase inhibitor and seprafilm were different, but their preventive effects were comparable. Thus, chymase inhibitor may represent a useful strategy for preventing abdominal adhesion in laparoscopic surgery.

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