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开发一种改良的腹膜粘连形成的离体模型,以及连接蛋白 43 在其发展中的作用。

Development of a refined ex vivo model of peritoneal adhesion formation, and a role for connexin 43 in their development.

机构信息

Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11, Mandalay Road, Singapore, 308232, Singapore.

Skin Research Institute Singapore, Level 17, Clinical Sciences Building, 11, Mandalay Road, Singapore, 308232, Singapore.

出版信息

Mol Cell Biochem. 2022 Jan;477(1):295-305. doi: 10.1007/s11010-021-04282-3. Epub 2021 Oct 29.

DOI:10.1007/s11010-021-04282-3
PMID:34716547
Abstract

Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly undesirable. We have developed a novel mouse peritoneal strip ex vivo adhesion model which may serve to bridge the gap between single cell culture systems and in vivo animal drug testing for the assessment of potential anti-adhesion agents, and study of causality of the process. We investigated the optimal conditions for adhesion formation with mouse peritoneal tissue strips by modifying an existing ex vivo rat model of peritoneal adhesions. We assessed the impact of the following conditions on the formation of adhesions: contact pressure, abrasions, and the presence of clotted blood. Macroscopic adhesions were detected in all mouse peritoneal strips exposed to specific conditions, namely abrasions and clotted blood, where peritoneal surfaces were kept in contact with pressure using cotton gauze in a tissue cassette. Adhesions were confirmed microscopically. Interestingly, connexin 43, a gap junction protein, was found to be upregulated at sites of adhesions. Key features of this model were the use of padding the abraded tissue with gauze and the use of a standardised volume of clotted blood. Using this model, peritoneal strips cultured with clotted blood between abraded surfaces were found to reproducibly develop adhesion bands at 72 h. Our goal is to develop a model that can be used in genetically modified mice in order to dissect out the role of particular genes in adhesion formation and to test drugs to prevent adhesion formation.

摘要

尽管外科科学取得了许多进展,但术后腹膜粘连仍然是现代手术中的一个相当大的风险,而且非常不理想。我们开发了一种新型的小鼠腹膜条体外粘连模型,该模型可能有助于弥合单细胞培养系统与体内动物药物测试之间的差距,用于评估潜在的抗粘连剂,并研究该过程的因果关系。我们通过修改现有的腹膜粘连大鼠体外模型,研究了形成粘连的最佳条件。我们评估了以下条件对粘连形成的影响:接触压力、磨损和凝血块的存在。所有暴露于特定条件(即磨损和凝血块)的小鼠腹膜条均检测到宏观粘连,其中腹膜表面使用纱布在组织盒中保持接触压力。粘连通过显微镜确认。有趣的是,连接蛋白 43(一种间隙连接蛋白)在粘连部位被上调。该模型的关键特征是使用纱布填充磨损的组织,以及使用标准化的凝血块体积。使用该模型,发现用凝血块培养在磨损表面之间的腹膜条在 72 小时内可重复性地形成粘连带。我们的目标是开发一种可用于基因修饰小鼠的模型,以剖析特定基因在粘连形成中的作用,并测试预防粘连形成的药物。

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引用本文的文献

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Connexin43 in Post-Surgical Peritoneal Adhesion Formation.缝隙连接蛋白43与术后腹膜粘连形成
Life (Basel). 2022 Oct 28;12(11):1734. doi: 10.3390/life12111734.

本文引用的文献

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Adhesions and Anti-Adhesion Systems Highlights.粘连与抗粘连系统要点
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Pelvic adhesions and fertility: Where are we in 2018?盆腔粘连与生育:2018年我们处于什么状况?
J Visc Surg. 2018 Jun;155 Suppl 1:S11-S15. doi: 10.1016/j.jviscsurg.2018.02.004. Epub 2018 May 18.
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Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.芍药苷可预防实验性大鼠模型术后腹膜粘连的形成。
Oncotarget. 2017 Sep 28;8(55):93899-93911. doi: 10.18632/oncotarget.21333. eCollection 2017 Nov 7.
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Effect of Resveratrol on the Prevention of Intra-Abdominal Adhesion Formation in a Rat Model.白藜芦醇对大鼠模型腹腔内粘连形成预防作用的研究
Cell Physiol Biochem. 2016;39(1):33-46. doi: 10.1159/000445603. Epub 2016 Jun 20.
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Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions.间皮-间充质转化在术后腹膜粘连发病机制中的作用
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Evaluation of 4DryField® PH as Adhesion Prevention Barrier Tested in an Optimized Adhesion Model in Rats.在大鼠优化粘连模型中对4DryField® PH作为粘连预防屏障的评估。
Eur Surg Res. 2015 Dec;55(4):341-351. doi: 10.1159/000441025. Epub 2015 Oct 28.
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The Creation of a Model for Ex Vivo Development of Postoperative Adhesions.术后粘连体外发育模型的创建。
Reprod Sci. 2016 May;23(5):610-2. doi: 10.1177/1933719115607997. Epub 2015 Sep 25.
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