Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Jan;392(1):37-43. doi: 10.1007/s00210-018-1560-y. Epub 2018 Sep 10.
Many pathways are involved in the association between biliary obstruction and liver injury. We investigated the intervention influence and effect of rosuvastatin (Rvs) on the high mobility group protein 1 (HMGB1)/toll-like receptor-4 (TLR4) axis and microRNA-21 (miR-21) in cholestatic liver injury. This model was performed by ligating common bile duct of Wistar rats. Saline and Rvs were orally administrated by gastric gavages. Liver and blood samples were collected and subjected to molecular and biochemical evaluation. We found that the daily oral administration of Rvs was protective against the occurrence of cholestatic liver injury. This was evident from the results of hepatic, oxidative stress, and inflammatory biomarkers. This study also revealed the Rvs inhibitory effect on the HMGB1/TLR4 intracellular signaling axis as evidenced by decreasing the levels of nuclear factor κβ (NFκβ), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) production. Furthermore, Rvs-treated group showed a significant reduction in the expression of miR-21 in comparison to the untreated group. Accordingly, rosuvastatin interference with the HMGB1/TLR4 and miR-21 expression could explain its hepatoprotective effect in cholestatic liver injury.
许多途径参与了胆汁淤积与肝损伤之间的关联。我们研究了瑞舒伐他汀（Rvs）对胆汁淤积性肝损伤中高迁移率族蛋白 1（HMGB1）/ toll 样受体 4（TLR4）轴和微小 RNA-21（miR-21）的干预影响和作用。该模型通过结扎 Wistar 大鼠的胆总管来建立。盐水和 Rvs 通过胃灌胃进行口服给药。采集肝和血液样本，并进行分子和生化评估。我们发现，Rvs 的每日口服给药可预防胆汁淤积性肝损伤的发生。这从肝、氧化应激和炎症生物标志物的结果中可以明显看出。这项研究还揭示了 Rvs 对 HMGB1/TLR4 细胞内信号通路的抑制作用，这表现在核因子 κβ（NFκβ）、肿瘤坏死因子 α（TNFα）和白细胞介素 6（IL6）产生的水平降低。此外，与未治疗组相比，Rvs 治疗组的 miR-21 表达明显降低。因此，Rvs 对 HMGB1/TLR4 和 miR-21 表达的干扰可以解释其在胆汁淤积性肝损伤中的保肝作用。
