Anti-fibrotic effect of thymoquinone on hepatic stellate cells
Anti-fibrotic effect of thymoquinone on hepatic stellate cells
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DOI：
10.1016/j.phymed.2013.09.014
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发表时间：
2014-02-15
期刊：
影响因子：
7.9
通讯作者：
Li, Song
中科院分区：
文献类型：
--
作者：
Ghazwani, Mohammed;Zhang, Yifei;Li, Song
肝星状细胞（hepatic stellate cells，HSC）是肝脏中参与细胞外基质生成的主要细胞类型。肝损伤后，HSC经历了从静止状态向活化状态的转分化过程，在肝纤维化中起重要作用。以往的研究表明，百里醌（TQ）可能有保护作用，对肝纤维化的动物模型，但其潜在的作用机制并不完全清楚。本研究的目的是研究TQ是否对HSC有任何直接影响。我们的研究结果表明，TQ预处理小鼠对CCl 4诱导的肝损伤具有保护作用，与对照组（未处理）相比，这与以前的研究一致。此外，我们的体内研究表明，TQ处理显著下调COL 1A 1和α-SMA mRNA水平。同样，体外研究证实，TQ下调活化的大鼠HSC和LX 2细胞（一种永生化的人肝星状细胞系）中的COL 1A 1、COL 3A 1和a-SMA mRNA水平。TQ预处理也抑制LPS诱导的LX 2细胞中的促炎反应，如通过降低IL-6和MCP-1的mRNA表达所证明的。从机制上讲，NF-κ B B通路的失活可能在TQ介导的HSC促炎反应抑制中发挥作用。最后，我们已经表明，TQ抑制新鲜分离的大鼠肝星状细胞的培养触发的转分化所示的几个纤维化相关基因的mRNA表达的显着下调。总之，我们的研究表明，TQ对HSC有直接作用，这可能有助于其整体抗纤维化作用。(C)2013年爱思唯尔有限公司。All rights reserved.
Hepatic stellate cells (HSCs) are the major cell type involved in the production of extracellular matrix in liver. After liver injury, HSCs undergo transdifferentiation process from quiescent state to activated state, which plays an important role in liver fibrosis. Previous studies have shown that thymoquinone (TQ) might have protective effect against liver fibrosis in animal models; however, the underlying mechanism of action is not fully understood. The aim of this study is to examine whether TQ has any direct effect on HSCs. Our results showed that pretreatment of mice with TQ has protective effect against CCl4-induced liver injury compared to control group (untreated), which is consistent with previous studies. Moreover, our in vivo study showed that COL1A1 and alpha-SMA mRNA levels were significantly downregulated by TQ treatment. Similarly, in vitro study confirmed that TQ downregulated COL1A1, COL3A1 and a-SMA mRNA levels in activated rat HSCs and LX2 cells, an immortalized human hepatic stellate cell line. Pretreatment with TQ also inhibited the LPS-induced proinflammatory response in LX2 cells as demonstrated by reduced mRNA expression of IL-6 and MCP-1. Mechanistically, inactivation of NF-kappa B pathway is likely to play a role in the TQ-mediated inhibition of proinflammatory response in HSCs. Finally, we have shown that TQ inhibited the culture-triggered transdifferentiation of freshly isolated rat HSCs as shown by significant downregulation of mRNA expression of several fibrosis-related genes. In conclusion, our study suggests that TQ has a direct effect on HSCs, which may contribute to its overall antifibrotic effect. (C) 2013 Elsevier GmbH. All rights reserved.