Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute ...Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute and chronic diseases. In the present study, we aimed to investigate the alleviation effect of quercetin on rat liver fibrosis and explore its mechanism of action. Healthy male SD rats were randomly divided into the normal group, model group, and quercetin group, with six rats in each group. Liver fibrosis was induced by intraperitoneal injection of 1 m L/kg carbon tetrachloride(50% v/v in olive oil) twice a week for 6 weeks, and quercetin(100 mg/kg/d) was administered orally in the 7th week until the end of the 12th week. Blood and liver samples were collected at 1 h after the last administration. Serum liver function parameters(AST, ALT, ALP, GGT, and TBA) were detected by an automatic biochemical analyzer. H&E, Masson, and Sirius red staining were used to observe the pathological morphology of liver tissue. Western blotting analysis was used to evaluate the expressions of liver fibrotic factors(TGF-β1, α-SMA, MMP2, and MMP9) and bile acid-related regulatory proteins(FXR, CYP7A1, CYP8B1, and CYP27A1). The oxidative stress markers(GSH, GSH-Px, GR, SOD, and MDA) in the liver tissue were detected using corresponding kits. The contents of bile acids in the liver tissue were determined by LC-MS/MS. The results showed that compared with the model group, quercetin treatment could significantly reduce serum AST, ALT, and TBA levels(P < 0.05). The fibrotic liver injury was significantly improved, and the expressions of fibrotic factors TGF-β1, α-SMA, MMP2, and MMP9 were significantly decreased(P < 0.05). Liver GSH, GSH-Px, GR, and SOD levels were significantly increased(P < 0.05), and the MDA level was significantly decreased(P < 0.05). The contents of hepatic bile acids were significantly decreased(P < 0.05), the expression of FXR was significantly increased(P < 0.05), and the expressions of CYP7A1 and CYP8B1 were significantly decreased(P < 0.05). This study suggested that quercetin could effectively alleviate carbon tetrachloride-induced liver fibrosis injury, and its mechanism of action was related to improving the liver’s ability to resist oxidative stress and reducing the expressions of fibrotic factors and bile acid synthesis.展开更多
文摘【目的】基于法尼醇X受体,探究MK571对肝脏胆汁酸合成的影响.【方法】按体质量将24只健康大鼠随机分为MK571低、中、高剂量组和对照组,每组6只,分别每天腹腔注射5、10、20 mg/kg MK571和等体积生理盐水,连续给药7 d。采用全自动生化分析仪检测血清肝功能生化指标;HE染色观察肝脏病理学变化;LC-MS/MS检测血清和肝脏胆汁酸含量;蛋白免疫印迹法检测大鼠肝脏胆汁酸相关调节蛋白表达。【结果】与对照组相比,MK571干预后,血清丙氨酸转氨酶(ALT)、总胆红素(TBIL)和总胆汁酸(TBA)含量均显著下降(P<0.05);病理结果显示肝脏出现炎症损伤;胆汁酸检测结果显示:血清和肝脏甘氨熊去氧胆酸、甘氨脱氧胆酸、甘氨脱氧胆酸、甘氨胆酸和鹅去氧胆酸含量均显著下降(P<0.05);此外蛋白免疫印迹法结果显示:法尼醇X受体(Farnesoid X receptor,FXR)和胆盐输出泵(Bile salt export pump,BSEP)表达量均显著上升(均P<0.05),而胆固醇-7α-羟化酶(Cholesterol-7α-hydroxylase,CYP7A1)、胆固醇-12α-羟化酶(Cholesterol-12α-hydroxylase,CYP8B1)和胆固醇-27α-羟化酶(Cholesterol-27α-hydroxylase,CYP27A1)表达量均显著下降(P<0.05)。【结论】MK571可以抑制肝脏胆汁酸合成,其作用机制可能与激活FXR,下调CYP27A1,CYP7A1和CYP8B1表达,上调BSEP表达有关。
基金Natural Science Foundations of China (Grant No. 81960680)Lanzhou Chengguan District Science and Technology Project (Grant No. 2019RCCX0039)Intra-hospital Fund of the First Hospital of Lanzhou University (Grant No. ldyyyn2018-10),China。
文摘Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute and chronic diseases. In the present study, we aimed to investigate the alleviation effect of quercetin on rat liver fibrosis and explore its mechanism of action. Healthy male SD rats were randomly divided into the normal group, model group, and quercetin group, with six rats in each group. Liver fibrosis was induced by intraperitoneal injection of 1 m L/kg carbon tetrachloride(50% v/v in olive oil) twice a week for 6 weeks, and quercetin(100 mg/kg/d) was administered orally in the 7th week until the end of the 12th week. Blood and liver samples were collected at 1 h after the last administration. Serum liver function parameters(AST, ALT, ALP, GGT, and TBA) were detected by an automatic biochemical analyzer. H&E, Masson, and Sirius red staining were used to observe the pathological morphology of liver tissue. Western blotting analysis was used to evaluate the expressions of liver fibrotic factors(TGF-β1, α-SMA, MMP2, and MMP9) and bile acid-related regulatory proteins(FXR, CYP7A1, CYP8B1, and CYP27A1). The oxidative stress markers(GSH, GSH-Px, GR, SOD, and MDA) in the liver tissue were detected using corresponding kits. The contents of bile acids in the liver tissue were determined by LC-MS/MS. The results showed that compared with the model group, quercetin treatment could significantly reduce serum AST, ALT, and TBA levels(P < 0.05). The fibrotic liver injury was significantly improved, and the expressions of fibrotic factors TGF-β1, α-SMA, MMP2, and MMP9 were significantly decreased(P < 0.05). Liver GSH, GSH-Px, GR, and SOD levels were significantly increased(P < 0.05), and the MDA level was significantly decreased(P < 0.05). The contents of hepatic bile acids were significantly decreased(P < 0.05), the expression of FXR was significantly increased(P < 0.05), and the expressions of CYP7A1 and CYP8B1 were significantly decreased(P < 0.05). This study suggested that quercetin could effectively alleviate carbon tetrachloride-induced liver fibrosis injury, and its mechanism of action was related to improving the liver’s ability to resist oxidative stress and reducing the expressions of fibrotic factors and bile acid synthesis.
