Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan 450004, P.R. China.
Department of Emergency Medicine, Zhengzhou Chinese Medicine Hospital, Zhengzhou, Henan 450007, P.R. China.
Mol Med Rep. 2019 Feb;19(2):841-850. doi: 10.3892/mmr.2018.9719. Epub 2018 Dec 4.
α‑lipoic acid (ALA) is a naturally occurring antioxidant with protective effects against various hepatic injuries. The aim of the present study was to investigate the mechanisms by which ALA protects the liver from carbon tetrachloride (CCl4)‑induced liver cirrhosis. The widely used liver cirrhosis rat model was established via an intraperitoneal injection of 2 mg/kg 50% CCl4, three times/week for 8 weeks. Simultaneously, 50 or 100 mg/kg ALA was orally administrated to the rats every day for 8 weeks. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected in the serum. The pathological liver injuries were analyzed using hematoxylin and eosin and Masson's trichrome staining. The principal factors involved in the transforming growth factor‑β (TGF‑β)/mothers against decapentaplegic homolog 9 (Smad3) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and in autophagy were examined using reverse transcription‑quantitative polymerase chain reaction or western blot analysis. The results demonstrated that the administration of ALA alleviated CCl4‑induced liver injury, as demonstrated by decreased ALT and AST activity, improved pathological injuries and reduced collagen deposition. The CCl4‑induced increase in TGF‑β and phosphorylated‑Smad3 expression levels was additionally inhibited by treatment with ALA. Furthermore, the administration of ALA reversed the CCl4‑induced upregulation of light chain 3II and Beclin‑1, and downregulation of p62. The CCl4‑induced suppression of the AKT/mTOR pathway was additionally restored following treatment with ALA. In combination, the results of the present study demonstrated that ALA was able to protect CCl4‑induced liver cirrhosis, an effect that may be associated with inactivation of the TGF‑β/Smad3 pathway and suppression of autophagy.
α-硫辛酸（ALA）是一种天然存在的抗氧化剂，具有保护各种肝损伤的作用。本研究旨在探讨 ALA 保护肝脏免受四氯化碳（CCl4）诱导的肝硬化的机制。通过每周三次腹腔内注射 2mg/kg 50% CCl4，建立了广泛使用的肝硬化大鼠模型，共 8 周。同时，将 50 或 100mg/kg ALA 每天口服给予大鼠，共 8 周。检测血清中丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的活性。用苏木精和伊红以及 Masson 三色染色分析肝病理损伤。使用逆转录-定量聚合酶链反应或 Western blot 分析检测转化生长因子-β（TGF-β）/母亲对抗 decapentaplegic 同源物 9（Smad3）和蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）途径以及自噬中涉及的主要因素。结果表明，ALA 减轻了 CCl4 诱导的肝损伤，表现为 ALT 和 AST 活性降低，病理损伤改善，胶原沉积减少。ALA 处理还抑制了 CCl4 诱导的 TGF-β和磷酸化 Smad3 表达水平的增加。此外，ALA 逆转了 CCl4 诱导的 LC3II 和 Beclin-1 的上调以及 p62 的下调。ALA 处理还恢复了 CCl4 诱导的 AKT/mTOR 途径的抑制。综上所述，本研究结果表明，ALA 能够保护 CCl4 诱导的肝硬化，其作用可能与 TGF-β/Smad3 途径失活和自噬抑制有关。
