Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, People's Republic of China.
Int Immunopharmacol. 2010 Mar;10(3):357-63. doi: 10.1016/j.intimp.2009.12.010. Epub 2009 Dec 28.
Fulminant hepatic failure (FHF) remains an extremely poor prognosis and high mortality; better treatments are urgently needed. Tetrandrine (TET), a traditional anti-inflammatory drug, has been reported to exhibit hepatoprotective activities in several liver injury models. We now investigated the effects and underlying mechanisms of TET on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced FHF in mice. TET (50, 100, and 200 mg/kg) was given intraperitoneally 1h before LPS/D-GalN injection in mice. The mortality and liver injury was evaluated subsequently. The results showed that administering TET to mice reduced mortality and improved liver injury induced by LPS/D-GalN in a dose-dependent manner. In addition, TET dose-dependently inhibited LPS/D-GalN-induced NF-kappaB activation, serum and hepatic tissues tumor necrosis factor-alpha (TNF-alpha) production, caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression. Our experimental data indicated that TET might alleviate the FHF induced by LPS/D-GalN through inhibiting NF-kappaB activation to reduce TNF-alpha production.
暴发性肝衰竭（FHF）仍然预后极差，死亡率高；迫切需要更好的治疗方法。汉防己甲素（TET）是一种传统的抗炎药物，据报道在几种肝损伤模型中具有保肝作用。我们现在研究了 TET 对脂多糖（LPS）和 D-半乳糖胺（D-GalN）诱导的小鼠 FHF 的作用及其潜在机制。TET（50、100 和 200mg/kg）在 LPS/D-GalN 注射前 1 小时腹腔内给药，随后评估死亡率和肝损伤。结果表明，TET 给药可降低 LPS/D-GalN 诱导的小鼠死亡率并改善肝损伤，呈剂量依赖性。此外，TET 剂量依赖性抑制 LPS/D-GalN 诱导的 NF-kappaB 激活、血清和肝组织肿瘤坏死因子-α（TNF-α）产生、半胱天冬酶-3 激活和肝细胞凋亡、髓过氧化物酶（MPO）活性、细胞间黏附分子-1（ICAM-1）和内皮细胞黏附分子-1（ECAM-1）表达。我们的实验数据表明，TET 可能通过抑制 NF-kappaB 激活来减少 TNF-α 的产生，从而减轻 LPS/D-GalN 诱导的 FHF。
