Department of Pathology, Faculty of Veterinary Medicine, Aydın Adnan Menderes University, Aydın, Turkey.
Department of Biochemistry, Faculty of Veterinary Medicine, Aydın Adnan Menderes University, Aydın, Turkey.
Mol Biol Rep. 2023 Oct;50(10):8483-8495. doi: 10.1007/s11033-023-08753-2. Epub 2023 Aug 28.
Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated.
After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5 mg/kg CORM-2, (iii) 5 mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7 days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression.
These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.
尽管低剂量一氧化碳（CO）给药已被证明在各种纤维化疾病中具有抗纤维化作用，但它对术后并发症之一的腹膜粘连（PA）的影响尚未阐明。在这项研究中，研究了一氧化碳释放三羰基二氯钌（II）二聚体（CORM-2）给药对 PA 形成的影响及其潜在作用的潜在因素。
在诱导 PA 后，将大鼠分为四组，每组 8 只。大鼠每天接受（i）二甲基亚砜：盐水溶液（1:10）作为载体，（ii）2.5 mg/kg CORM-2，（iii）5 mg/kg CORM-2，或（iv）无效（i）CORM（iCORM）灌胃，持续 7 天。指定为假对照的大鼠（n = 8）未诱导 PA。进行大体、组织学、免疫组织化学和定量实时聚合酶链反应分析，以评估 CORM-2 给药的效果。大体分析表明，与用载体处理的大鼠相比，CORM-2 给药减少了 PA 的形成。组织学和免疫组织化学检查显示，在用 CORM-2 处理的大鼠的腹膜纤维化区域中，胶原沉积增加、肌成纤维细胞积累、微血管密度和 M1 巨噬细胞计数增加，而缺氧诱导的 Hif1a、促纤维化 Tgfb1、ECM 成分 Col1a1 和 Col3a1、胶原降解抑制剂 Timp1、纤维蛋白溶解抑制剂 Serpine1 和促炎 Tnf mRNA 表达减少，同时增加 M2 巨噬细胞标志物 Arg1 mRNA 表达。
这些结果表明，CORM-2 给药通过影响黏附发生过程，如促炎反应、纤维蛋白溶解系统、血管生成和纤维化，减少 PA 的形成。
