Kabirifar Razieh, Ghoreshi Zohreh-Al-Sadat, Safari Fatemeh, Karimollah Alireza, Moradi Ali, Eskandari-Nasab Ebrahim
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Hepatobiliary Pancreat Dis Int. 2017 Feb;16(1):88-95. doi: 10.1016/s1499-3872(16)60164-9.
Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model.
We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively.
Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P<0.05); quercetin treatment reversed these variables back toward normal (P<0.05). Another interesting finding was that the antioxidant markers e.g. superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P<0.05).
Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.
胆管结扎（BDL）及随后的胆汁淤积与氧化应激、肝细胞损伤和纤维化相关。槲皮素是一种具有抗纤维化和肝脏保护特性的黄酮类化合物。然而，槲皮素介导肝脏保护的分子机制尚未完全明确。本研究旨在评估槲皮素在BDL大鼠模型中发挥肝脏保护作用的机制。
将雄性Wistar大鼠分为4组（每组n = 8）：假手术组、假手术 + 槲皮素组（每天30 mg/kg）、BDL组和BDL + 槲皮素组（每天30 mg/kg）。四周后，处死大鼠，采集血液用于检测肝酶，采集肝脏分别通过定量PCR和蛋白质印迹法检测Rac1、Rac1 - GTP和NOX1的mRNA及蛋白质水平。
组织学检查和肝酶降低表明，槲皮素显著减轻了BDL大鼠的肝损伤。此外，与假手术组相比，BDL大鼠中Rac1、Rac1 - GTP和NOX1的mRNA及蛋白质表达显著增加（P < 0.05）；槲皮素治疗使这些指标恢复至正常水平（P < 0.05）。另一个有趣的发现是，与BDL大鼠相比，经槲皮素治疗的BDL大鼠中抗氧化标志物如超氧化物歧化酶和过氧化氢酶升高（P < 0.05）。
槲皮素通过增强肝组织的抗氧化能力，同时抑制Rac1、Rac1 - GTP和NOX1蛋白的产生，对BDL诱导的肝损伤具有肝脏保护活性。
