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新型大鼠腹膜粘连模型中糜酶抑制剂与透明质酸/羧甲基纤维素(施沛特)的比较。

Comparison of a chymase inhibitor and hyaluronic acid/carboxymethylcellulose (Seprafilm) in a novel peritoneal adhesion model in rats.

机构信息

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.

Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, Takatsuki, Japan.

出版信息

PLoS One. 2019 Jan 25;14(1):e0211391. doi: 10.1371/journal.pone.0211391. eCollection 2019.

Abstract

Adhesion formation that occurred after alkali-induced injury of the cecum was used as a novel adhesion model in rats, and it was compared with that of a common adhesion model after abrading the cecum. Using the novel adhesion model, inhibition of adhesion formation by a chymase inhibitor, Suc-Val-Pro-PheP(OPh)2, and by sodium hyaluronate/carboxymethylcellulose (Seprafilm) was evaluated, and their mechanisms were assessed. The degree of adhesion formation was more severe and more stable in the alkali-induced injury model than in the abrasion-induced injury model. Both the chymase inhibitor and Seprafilm showed significant attenuation of the degree of adhesion 14 days after alkali-induced injury. Chymase activity in the cecum was significantly increased after alkali-induced injury, but it was significantly attenuated by the chymase inhibitor and Seprafilm. Myeloperoxidase and transforming-growth factor (TGF)-β levels were significantly increased after alkali-induced injury, but they were attenuated by both the chymase inhibitor and Seprafilm. At the level of the adhesions, the numbers of both chymase-positive cells and TGF-β-positive cells were significantly increased, but their numbers were reduced by the chymase inhibitor and Seprafilm. In conclusion, a chymase inhibitor attenuated the degree of adhesions to the same degree as Seprafilm in a novel peritoneal adhesion model that was more severe and more stable than the common adhesion model, and not only the chymase inhibitor, but also Seprafilm reduced the chymase increase at the adhesions.

摘要

以大鼠盲肠碱损伤后形成的粘连作为一种新的粘连模型,与盲肠磨损后形成的常见粘连模型进行比较。使用新的粘连模型,评估糜酶抑制剂 Suc-Val-Pro-PheP(OPh)2 和透明质酸钠/羧甲基纤维素(Seprafilm)对粘连形成的抑制作用,并评估其机制。碱损伤模型中粘连形成的程度比磨损损伤模型更严重且更稳定。糜酶抑制剂和 Seprafilm 均能显著减轻碱损伤 14 天后粘连的程度。碱损伤后盲肠糜酶活性显著增加,但糜酶抑制剂和 Seprafilm 显著降低了其活性。碱损伤后髓过氧化物酶和转化生长因子(TGF)-β水平显著升高,但糜酶抑制剂和 Seprafilm 均可降低其水平。在粘连部位,阳性细胞的数量显著增加,但是用糜酶抑制剂和 Seprafilm 处理后,阳性细胞的数量减少。总之,糜酶抑制剂在一种比常见粘连模型更严重且更稳定的新型腹膜粘连模型中,对粘连程度的抑制作用与 Seprafilm 相同,而且不仅糜酶抑制剂,Seprafilm 也能减少粘连处的糜酶增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1f/6347210/ee5605803133/pone.0211391.g001.jpg

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