Department of Obstetrics and Gynecology, Chung-Ang University School of Medicine, Seoul 06974, Republic of Korea.
Department of Physiology, Chung-Ang University School of Medicine, Seoul, Republic of Korea.
Biomed Res Int. 2023 Jan 12;2023:4050730. doi: 10.1155/2023/4050730. eCollection 2023.
Intra-abdominal adhesion is a complication following abdominal surgery caused by the suppression of fibrinolytic activity and aggravated fibroblast invasion of the injured area, which may lead to chronic illnesses such as chronic pain, intestinal obstruction, and female infertility. This study hypothesized that lumbrokinase, a fibrinolytic enzyme extracted from the earthworm, supports the wound healing process. Therefore, we assessed the effect of lumbrokinase on intra-abdominal adhesion. Lumbrokinase treatment significantly decreased the severity and the area of intra-abdominal adhesion in a dose-dependent manner compared with the controls (untreated and hyaluronate-treated). Lumbrokinase-associated adverse effects were not observed. Immunohistochemical analysis of adhesion tissues revealed a loosened adhesive band between tissues, coupled with significantly decreased peritoneal thickening in the lumbrokinase-treated group versus the control group. Three-dimensional spheroid, MTT, and scratch wound migration assays using the IMR-90 human fibroblast cell line demonstrated that lumbrokinase significantly attenuated the migration and adhesive activity of fibroblasts without compromising cell proliferation. The luciferase assay and western blot analysis showed that lumbrokinase inhibited the AP-1/ICAM-1 cell adhesion signaling pathway. Therefore, lumbrokinase decreases intra-abdominal adhesion and peritoneal thickening by augmenting fibrinolytic action and inhibiting fibroblast migration and adhesive activity via attenuation of the AP-1/ICAM-1 signaling pathway. Lumbrokinase is thus a promising agent to prevent intra-abdominal adhesion.
腹腔粘连是腹部手术后的一种并发症，是由于纤溶活性受到抑制和纤维母细胞侵入受伤区域加重所致，可能导致慢性疼痛、肠梗阻和女性不孕等疾病。本研究假设从蚯蚓中提取的纤溶酶蚓激酶有助于伤口愈合过程。因此，我们评估了蚓激酶对腹腔粘连的影响。蚓激酶治疗组与对照组（未治疗组和透明质酸钠治疗组）相比，腹腔粘连的严重程度和面积呈剂量依赖性降低。未观察到与蚓激酶相关的不良反应。粘连组织的免疫组织化学分析显示，组织之间的粘合带变松，蚓激酶治疗组与对照组相比，腹膜增厚明显减少。使用 IMR-90 人成纤维细胞系进行的三维球体、MTT 和划痕伤口迁移试验表明，蚓激酶显著减弱了成纤维细胞的迁移和粘附活性，而不影响细胞增殖。荧光素酶测定和 Western blot 分析表明，蚓激酶通过抑制 AP-1/ICAM-1 细胞黏附信号通路来抑制纤溶酶原激活物抑制物-1 的活性。因此，蚓激酶通过增强纤溶作用和抑制纤维母细胞迁移和粘附活性来减少腹腔粘连和腹膜增厚，通过抑制 AP-1/ICAM-1 信号通路。因此，蚓激酶是一种有前途的预防腹腔粘连的药物。
