The present study was designed to investigate the potential protective effects of diosmin (DS) and/or sildenafil against bile duct ligation (BDL). In order to achieve this goal, BDL was performed to induce liver cirrhosis, DS (100 mg/kg/day, p.o.) and sildenafil (10 mg/kg, twice daily, p.o.) were administrated alone or in combination 24 h after the surgical operation and lasted for 4 weeks. Liver function biomarkers, fibrotic markers, oxidative stress markers, mRNA expression of NF-κB-p65, P₃₈-MAPK, Nrf-2, and Keap-1, as well as protein expression of cytoglobin, NF-κB-p65, Nrf-2, iNOS and eNOS were investigated concomitantly with histopathological study. The results revealed that, 4 weeks of BDL induced a significant alteration in liver functions, fibrotic and oxidative stress markers. Furthermore, up-regulation of NF-κB-p65, P₃₈-MAPK, Keap-1 and iNOS concomitantly with down-regulation of Nrf-2, cytoglobin and eNOS expressions were observed after BDL. DS and/or sildenafil treatment significantly alleviated the disturbance induced by BDL. These findings were further supported by the improvement in histopathological features. Additionally, co-administration of DS and sildenafil were found to significantly improved liver defects due to BDL as compared to the individual drugs. It can be concluded that, DS and sildenafil exhibit hepatoprotective effects through modulation of Keap-1/Nrf-2 and P₃₈-MAPK/NF-κB/iNOS pathway.

本研究旨在调查地高辛（DS）和/或西地那非对胆管结扎（BDL）的潜在保护作用。为了实现这一目标，进行了BDL诱导肝硬化，在手术后24小时单独或联合使用DS（100 mg / kg /天，口服）和西地那非（10 mg / kg，每天两次，口服）手术持续了四个星期。肝功能生物标志物，纤维化标志物，氧化应激标志物，NF-κB-p65，P _38的mRNA表达对MAPK，Nrf-2和Keap-1以及细胞蛋白，NF-κB-p65，Nrf-2，iNOS和eNOS的蛋白质表达进行了组织病理学研究。结果显示，BDL的4周诱导了肝功能，纤维化和氧化应激标志物的显着改变。此外，NF-κB-p65，P ₃₈的上调-MAPK，Keap-1和iNOS伴随Nrf-2的下调，BDL后观察到细胞蛋白和eNOS的表达。DS和/或西地那非治疗显着减轻了由BDL引起的干扰。这些发现得到了组织病理学特征的改善的进一步支持。另外，与单独的药物相比，发现DS和西地那非的共同给药可显着改善由于BDL引起的肝脏缺陷。可以得出结论，DS和西地那非可通过调节Keap-1 / Nrf-2和P ₃₈ -MAPK /NF-κB/ iNOS途径发挥肝保护作用。