PDF(Pubmed)
Abstract：
The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body\'s storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil\'s hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl4). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl4 by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1β, osteopontin (OPN), and transforming growth factor-β (TGF-β)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl4 through suppressing OPN.
摘要：
肝脏执行许多基本任务，比如合成胆固醇，控制体内糖原的储存，解毒代谢物，除了表演，调节体内平衡。肝纤维化是以包括胶原纤维的细胞外基质(ECM)过度积累为特征的病理状态。西地那非（5型磷酸二酯酶的选择性抑制剂）具有抗炎，抗氧化和抗凋亡特性。它通常用于治疗男性勃起功能障碍。当前研究的目的是评估西地那非对四氯化碳（CCl4）引起的大鼠肝纤维化的肝保护潜力。确定了肝酶和氧化标记以及促纤维化基因。结果表明，西地那非通过恢复正常ALT水平减轻CCl4引起的肝功能障碍，AST,和GGT以及通过恢复增加的谷胱甘肽（GSH）所证明的抗氧化剂状态，还有过氧化氢酶.此外,a显著下调促纤维化基因的mRNA表达[胶原蛋白-1α，IL-1β,骨桥蛋白（OPN），和转化生长因子-β（TGF-β）]。此外,西地那非减轻肝小叶之间的门静脉纤维化，中央静脉的充血和扩张，和炎症细胞浸润。因此,据推测,西地那非可能通过抑制OPN,有助于控制CCl4引起的肝毒性.
