Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-κB and IFN-γ/STAT1 pathways
Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-κB and IFN-γ/STAT1 pathways
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DOI：
10.1007/s10875-008-9206-3
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发表时间：
2008-09-01
影响因子：
9.1
通讯作者：
Xu, Lingyun
中科院分区：
文献类型：
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作者：
Xu, Yan;Feng, Dechun;Xu, Lingyun
丹参酮Ⅱ A磺酸钠（STS）是丹参的主要药理活性成分丹参酮Ⅱ A的水溶性衍生物。本研究的目的是探讨STS对刀豆球蛋白A（ConA）诱导的小鼠肝炎（CIH）的影响，免疫介导的肝损伤的实验模型。结果与对照组小鼠相比，STS预处理C57 BL/6小鼠释放更少的丙氨酸转氨酶到血浆中的ConA的挑战，并有减少炎症浸润和肝细胞凋亡。因此，STS保护小鼠免受CIH。在STS预处理的小鼠诱导CIH，我们发现废除肿瘤坏死因子-α和干扰素（IFN）-γ的生产。此外，这些小鼠中IFN诱导蛋白-10和巨噬细胞炎性蛋白-1 α的mRNA表达降低。STS的抗炎作用机制可能与其对NF-κ B和IFN-γ/STAT 1等重要炎症信号通路的调节有关。结论STS对免疫性肝损伤小鼠具有保护作用。这种保护作用与其通过调节NF-κ B和IFN-γ/IFN-γ抑制重要炎症介质的产生有关。STAT 1信号通路。
Introduction Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury.Results C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1 alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappa B and IFN-gamma/STAT1.Conclusion In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-kappa B and IFN-gamma/STAT1 signaling pathways.