Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University (Girls), Nasr City, Cairo 11884, Egypt.
J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):89-94. doi: 10.1002/jbt.20315.
Recent studies reported that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have pleotropic effects independent of their lipid-lowering properties. The present study was undertaken to determine whether treatment with rosuvastatin (RO) would be beneficial in a rat model of bile duct ligation (BDL). Animals were divided into three groups: a sham group (group I), a BDL group treated with vehicle (group II), and a BDL group treated with RO (10 mg/kg) (group III). Serum levels of total bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase decreased significantly in group III when compared to group II. Lipid peroxides and NO levels of group III were found to be significantly lower than those of group II. Antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and catalase) activity in liver tissues markedly decreased in group II, whereas treatment with RO preserved antioxidant enzyme activity. DT-diaphorase activity in group II was significantly higher than that in group III. The histopathological results showed multiple numbers of newly formed bile ductules with inflammatory cells infiltration in group II. These pathological changes were improved in group III. Our data indicate that RO ameliorates hepatic injury, inflammation, lipid peroxidation and increases antioxidant enzymes activity in rats subjected to BDL. RO may have a beneficial effect on treatment of cholestatic liver diseases.
最近的研究报道，3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂具有独立于其降脂特性的多效作用。本研究旨在确定在胆管结扎（BDL）大鼠模型中，使用罗苏伐他汀（RO）治疗是否有益。动物分为三组：假手术组（I 组）、用载体治疗的 BDL 组（II 组）和用 RO（10mg/kg）治疗的 BDL 组（III 组）。与 II 组相比，III 组的血清总胆红素、γ-谷氨酰转肽酶、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平显著降低。III 组的脂质过氧化物和 NO 水平明显低于 II 组。II 组肝组织抗氧化酶（超氧化物歧化酶、谷胱甘肽-S-转移酶和过氧化氢酶）活性明显降低，而 RO 治疗则保留了抗氧化酶活性。II 组的 DT-黄递酶活性明显高于 III 组。组织病理学结果显示，II 组有大量新生胆管和炎症细胞浸润。这些病变在 III 组得到改善。我们的数据表明，RO 可改善胆管结扎大鼠的肝损伤、炎症、脂质过氧化和增加抗氧化酶活性。RO 可能对治疗胆汁淤积性肝病有益。
