Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.
Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China.
Mediators Inflamm. 2019 Jul 31;2019:6175091. doi: 10.1155/2019/6175091. eCollection 2019.
Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin.
Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction.
Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor 1 (TGF-1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways.
Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-1-mediated Smad3 and p38 MAPK signaling pathways.
肝纤维化是慢性肝损伤导致的创伤愈合反应的结果，如果得不到控制，可能会发展为肝硬化。本研究探讨了山奈酚对肝纤维化的保护作用。
通过腹腔注射四氯化碳（CCl）或胆管结扎（BDL）建立肝纤维化小鼠模型。山奈酚 10 或 30mg/kg 通过灌胃每周 5 天给药 8 周，在 CCl 模型中给药 2 周。通过 Western blot、免疫组化和实时定量聚合酶链反应测定蛋白质和 mRNA 的表达。
山奈酚在两种模型中均显著抑制肝纤维化，抑制肝星状细胞（HSC）激活、细胞外基质（ECM）沉积和自噬。这些作用与下调转化生长因子 1（TGF-1）介导的 Smad3 和 p38 丝裂原活化蛋白激酶（MAPK）信号通路有关。
山奈酚通过抑制 TGF-1 介导的 Smad3 和 p38 MAPK 信号通路，减少 ECM 形成和自噬，从而预防肝纤维化。
