Yiqi-Huoxue Granule (YQHX) Downregulates Prothrombotic Factors by Modulating KLF2 and NF-κB in HUVECs following LPS Stimulation
Yiqi-Huoxue Granule (YQHX) Downregulates Prothrombotic Factors by Modulating KLF2 and NF-κB in HUVECs following LPS Stimulation
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DOI：
10.1155/2019/9425183
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发表时间：
2019-02
影响因子：
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通讯作者：
Hong Wu;Xinzhou Wang;Shuibo Gao;Liping Dai;Haibin Tong;Haixia Gao;Zhen Lei;Yongjun Han;Zhentao Wang;Lihua Han;D. Qi
中科院分区：
文献类型：
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作者：
Hong Wu;Xinzhou Wang;Shuibo Gao;Liping Dai;Haibin Tong;Haixia Gao;Zhen Lei;Yongjun Han;Zhentao Wang;Lihua Han;D. Qi
益气活血颗粒是一种在我国广泛应用于治疗气虚、血瘀证的中药。这些症状都与炎症有关，但YQHX对抗炎症的机制在很大程度上是未知的。因此，本研究探讨了益气活血方对脂多糖（LPS）诱导的HUVECs炎症反应的调节作用。结果表明，益气活血方能显著抑制血栓形成前因子纤溶酶原激活物抑制剂-1（派-1）和组织因子（TF）的产生，上调Kruppel样因子2（KLF 2）的蛋白表达。通过用Lenti-shKLF 2载体在KLF 2中的转基因敲低，派-1和TF的增加显著减弱。YQHX还能降低LPS刺激后核因子-κB（NF-κB）p65和IκB的磷酸化，并通过NF-κ B依赖的机制有效抑制派-1和TF。以上结果提示，YQHX通过调节KLF 2表达和NF-κB信号通路发挥抗血栓作用。KLF 2和NF-κB可能是动脉粥样硬化相关炎症的潜在治疗靶点。
The Yiqi-Huoxue granule (YQHX) is a traditional Chinese medication widely used in the therapy of the traditional Chinese medicine diagnosis “Qi deficiency” or “blood stasis” in China. Both these symptoms are related to inflammation, but the mechanisms of YQHX against inflammation are largely unknown. Thus, our present study investigated the effects of YQHX on regulating inflammatory responses induced by lipopolysaccharides (LPS) in HUVECs. Our data found that YQHX remarkably inhibits the production of prothrombotic factors, plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF), while it upregulates the protein expression of Kruppel-like factor 2 (KLF2). The increase in PAI-1 and TF was significantly attenuated through a transgenic knockdown in KLF2 with a Lenti-shKLF2 vector. YQHX also decreases the phosphorylation of nuclear factor-κB (NF-κB) p65 and IκB following LPS stimulation, and it effectively suppresses PAI-1 and TF via a NF-κB-dependent mechanism. Taken together, our results suggest that YQHX provides a notable antithrombotic activity via regulating the KLF2 expression and NF-κB signaling pathway in HUVECs. The KLF2 and NF-κB may be potential therapeutic targets for interventions of inflammation associated with atherosclerosis.