Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway.
Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway.
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丹参酮 IIA 磺酸钠通过阻断 MAPK/HIF-1 α 信号通路的激活来减少香烟烟雾引起的炎症和氧化应激
DOI：
10.3389/fphar.2018.00263
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发表时间：
2018
影响因子：
5.6
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Guan R;Wang J;Li Z;Ding M;Li D;Xu G;Wang T;Chen Y;Yang Q;Long Z;Cai Z;Zhang C;Liang X;Dong L;Zhao L;Zhang H;Sun D;Lu W
缺氧诱导因子 (HIF)-1α 的异常激活是慢性阻塞性肺疾病 (COPD) 中经常遇到的情况，并会促进氧化应激和炎症。本研究调查了丹参酮 IIA 磺酸钠 (STS)（丹参酮 IIA 的水溶性衍生物）是否可以通过抑制 HIF-1α 诱导的香烟烟雾 (CS) 诱导的慢性阻塞性肺病小鼠氧化应激和炎症来发挥作用。在这里，我们发现 STS 可以改善暴露于 CS 的小鼠的肺功能，改善肺气肿并减少肺部炎症细胞的浸润。 STS 减少了 CS 和香烟烟雾提取物 (CSE) 诱导的肺部和巨噬细胞中肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-1β 的上调。 STS 还抑制 CSE 诱导的活性氧 (ROS) 产生，以及巨噬细胞中血红素加氧酶 (HO)-1、NOX1 和基质金属蛋白酶 (MMP)-9 的上调。此外，STS 在体内和体外抑制 HIF-1α 表达，并且用 HIF-1α siRNA 预处理可降低 CSE 诱导的巨噬细胞中 TNF-α、IL-1β 和 HO-1 含量的升高。此外，我们发现STS抑制CSE诱导的巨噬细胞中ERK、p38 MAPK和JNK的磷酸化，并且抑制这些信号分子显着抑制CSE诱导的HIF-1α表达。这表明STS可能通过阻断MAPK信号传导来抑制CSE诱导的HIF-1α表达。此外，STS 还促进 CSE 刺激的巨噬细胞中 HIF-1α 蛋白的降解。综上所述，这些结果表明 STS 可能通过抑制 HIF-1α 信号传导来预防 COPD 的发展，并且可能是治疗 COPD 的一种新策略。
Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.
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DOI：
10.3390/molecules22040644
发表时间：
2017-04-17
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chen SJ;Cui MC
通讯作者：
Cui MC
大黄素通过抑制上皮间质转化和成纤维细胞活化改善博莱霉素诱导的大鼠肺纤维化
影响因子：
4.6
作者：
Guan R;Wang X;Zhao X;Song N;Zhu J;Wang J;Wang J;Xia C;Chen Y;Zhu D;Shen L
通讯作者：
Shen L
大黄素减轻博莱霉素诱导的大鼠肺纤维化
影响因子：
3.5
作者：
Guan, Ruijuan;Zhao, Xiaomei;Shen, Linlin
通讯作者：
Shen, Linlin
影响因子：
3.7
作者：
Bewley MA;Belchamber KB;Chana KK;Budd RC;Donaldson G;Wedzicha JA;Brightling CE;Kilty I;Donnelly LE;Barnes PJ;Singh D;Whyte MK;Dockrell DH;COPDMAP
通讯作者：
COPDMAP
影响因子：
4.1
作者：
Frede, Stilla;Stockmann, Christian;Fandrey, Joachim
通讯作者：
Fandrey, Joachim