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