Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-κB activation
Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-κB activation
复制标题
粉防己碱通过抑制 NF-kappaB 激活来保护小鼠免受伴刀豆球蛋白 A 诱导的肝炎。
DOI：
10.1016/j.imlet.2008.10.001
复制
发表时间：
2008-12-22
影响因子：
4.4
通讯作者：
Xu, Lingyun
中科院分区：
文献类型：
--
作者：
Feng, Dechun;Mei, Yunhua;Xu, Lingyun
汉防己甲素（Tetrandrine，泰特）是中药粉防己（Stephania tetrandra S摩尔）的主要活性成分，传统上用于治疗风湿性疾病、矽肺和高血压。刀豆球蛋白A（ConA）诱导的肝炎（ConA-induced hepatitis，CIH）是一种T细胞依赖性肝炎，是研究免疫介导的肝毒性机制和治疗的理想动物模型。本研究旨在探讨泰特对CIH小鼠的保护作用。C57 BL/6小鼠经泰特预处理后，注射ConA诱导CIH。肝损伤进行了生化和组织学评估。测定血浆细胞因子水平和肝脏中趋化因子信使RNA（mRNA）的表达。我们发现，用泰特预处理小鼠可显著降低血浆转氨酶释放和肝损伤的严重程度。我们进一步研究了泰特的保护作用机制。用泰特预处理CIH小鼠，可显著降低血浆TNF-α、IFN-γ、IL-12和IL-4浓度的升高，同时降低肝脏中IFN-诱导蛋白-10和巨噬细胞炎性蛋白-1 α的表达。此外，泰特通过阻止I κ B α激酶a的活化，抑制上述炎性细胞因子的关键转录因子NF-κ B活性。(IKKα），然后抑制I κ B α的磷酸化以稳定肝内白细胞中的I κ B α。总之，泰特能够预防体内T细胞介导的肝损伤。有益效果可能取决于通过抑制NF-κ B活化来抑制肝脏中各种炎症介质的产生。(C)2008 Elsevier B. V.保留所有权利。
Tetrandrine (TET) is the major pharmacologically active compound of Chinese herb Stephania tetrandra S Moore, which has been used traditionally for the treatment of rheumatic disorders, silicosis and hypertension, Concanavalin A (ConA)-induced hepatitis (CIH) is a T-cell-dependent hepatitis and a well-established animal model for studying the mechanisms and therapy of immune-mediated hepatotoxicity. The aim of this study was to investigate whether TET could protect mice from CIH. C57BL/6 mice were injected with ConA to induce CIH pretreated with or without TET. Liver injury was assessed biochemically and histologically. Levels of plasma cytokines and the expressions of chemokine messenger RNA (mRNA) in the liver were determined. We found that pretreatment of mice with TET markedly reduced plasma transaminase release and the severity of liver damage. We further investigated the mechanisms of the protective effects of TET. When CIH-induced mice pretreated with TET, the increases of plasma concentrations of TNF-alpha, IFN-gamma, IL-12 and IL-4 were dramatically attenuated: at the same time, IFN-inducible protein-10 and macrophage inflammatory protein-1 a expressions in liver were decreased. Furthermore, TET inhibited NF-kappa B activity, the critical transcriptional factor of the above mentioned inflammatory cytokines, by preventing the activation Of I kappa B alpha kinasea. (IKK alpha) and then inhibiting phosphorylation Of I kappa B alpha to stabilize I kappa B alpha in intrahepatic leukocytes. In conclusion, TET is able to prevent T-cell-mediated liver injury in vivo. The beneficial effect may depend on suppressing the production of various inflammatory mediators in the liver through inhibiting of NF-kappa B activation. (C) 2008 Elsevier B.V. All rights reserved.